Journal articles on the topic 'Arteriolar myogenic tone'
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1
Davis, Michael J., and Judy Davidson. "Force-velocity relationship of myogenically active arterioles." American Journal of Physiology-Heart and Circulatory Physiology 282, no. 1 (January 1, 2002): H165—H174. http://dx.doi.org/10.1152/ajpheart.2002.282.1.h165.
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We compared the shortening velocity of smooth muscle in arterioles that had low or high levels of myogenic tone or norepinephrine (NE)-induced tone. We hypothesized that enhanced myogenic tone of arterioles reflects an enhanced maximum velocity of shortening of arteriolar smooth muscle in a way that is different from that produced by NE. These concepts are untested assumptions of arteriolar mechanics. Second-order arterioles from hamster cheek pouch (passive diameter at 40 mmHg = 42 μm) were isolated and cannulated for in vitro study. In the absence of flow, pressure was controlled by hydraulic pumps so that servo control of wall tension could be achieved from measurement of internal diameter and pressure. Isotonic quick-release protocols were used to measure the initial velocity of shortening following release from control wall tension (afterload) to a series of fractional afterloads. After release, the initial rates of shortening were fit to the Hill equation to obtain coefficients for a hyperbolic fit of the velocity-afterload relationship. The maximal unloaded shortening velocity for partially activated arterioles ( V′max) was determined from the y-intercept of each plot. Using this procedure, we compared V′max from two groups of arterioles equilibrated at low or high pressure, i.e., with low or high myogenic tone. Arterioles with higher myogenic tone had higher values of V′max than arterioles with lower myogenic tone. V′max for arterioles partially activated with NE at low pressure was comparable to V′max for arterioles with high myogenic tone, but NE produced high velocities at low force, whereas enhanced myogenic tone produced roughly parallel shifts in velocity and force. The results suggest that increased myogenic tone does indeed reflect enhanced activation of arteriolar smooth muscle, and this effect is mechanically different from that produced by NE.
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Spurrell, Brian E., Timothy V. Murphy, and Michael A. Hill. "Tyrosine phosphorylation modulates arteriolar tone but is not fundamental to myogenic response." American Journal of Physiology-Heart and Circulatory Physiology 278, no. 2 (February 1, 2000): H373—H382. http://dx.doi.org/10.1152/ajpheart.2000.278.2.h373.
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The present study investigated the role of protein tyrosine phosphorylation in myogenic responsiveness of rat skeletal muscle arterioles. Arteriolar segments were cannulated and pressurized without intraluminal flow. All vessels studied developed spontaneous tone and demonstrated significant myogenic constriction to step changes in pressure with a resultant increase in myogenic tone over an intraluminal pressure range of 50–150 mmHg. Step increases in intraluminal pressure from 50 to 120 mmHg caused a rapid and sustained elevation in intracellular [Ca2+], as measured using fura 2. Vessels with myogenic tone dilated in response to tyrosine kinase inhibitors genistein (10 or 30 μM) and tyrphostin A47 (10 or 30 μM) and constricted to the tyrosine phosphatase inhibitor pervanadate (1 or 10 μM). Despite the dilator effect, myogenic reactivity was not blocked by the inhibitors. Daidzein (10 μM), a compound structurally similar to genistein but without tyrosine kinase-inhibiting activity, did not alter vessel tone or myogenic responses. Preincubation of arterioles with genistein or tyrphostin A47 did not significantly alter baseline arteriolar [Ca2+], and neither drug reduced the increase in [Ca2+] following an acute increase in intraluminal pressure. Constriction induced by pervanadate (10 μM) was not accompanied by a significant increase in intracellular [Ca2+], even though removal of extracellular Ca2+ reversed the constriction. Examination of smooth muscle tyrosine phosphorylation, using a fluorescent phosphotyrosine antibody and confocal microscopy, showed that increased intraluminal pressure resulted in an increase in anti-phosphotyrosine fluorescence. Because manipulation of tyrosine kinase activity was found to alter vessel diameter, these data support a role for tyrosine phosphorylation in modulation of arteriolar tone. However, the results indicate that acute arteriolar myogenic constriction does not require tyrosine phosphorylation.
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Heaps, Cristine L., and Douglas K. Bowles. "Nonuniform changes in arteriolar myogenic tone within skeletal muscle following hindlimb unweighting." Journal of Applied Physiology 92, no. 3 (March 1, 2002): 1145–51. http://dx.doi.org/10.1152/japplphysiol.01031.2000.
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Hindlimb unweighting (HLU) has been shown to alter myogenic tone distinctly in arterioles isolated from skeletal muscles composed predominantly of fast-twitch (white gastrocnemius) compared with slow-twitch (soleus) fibers. Based on these findings, we hypothesized that HLU would alter myogenic tone differently in arterioles isolated from distinct fiber-type regions within a single skeletal muscle. We further hypothesized that alterations in myogenic tone would be associated with alterations in voltage-gated Ca2+ channel current (VGCC) density of arteriolar smooth muscle. After 14 days of HLU or weight bearing (control), first-order arterioles were isolated from both fast-twitch and mixed fiber-type regions of the gastrocnemius muscle, cannulated, and pressurized at 90 cmH2O. Mixed gastrocnemius arterioles of HLU rats demonstrated increased spontaneous tone [43 ± 5% (HLU) vs. 27 ± 4% (control) of possible constriction] and an approximately twofold enhanced myogenic response when exposed to step changes in intraluminal pressure (10–130 cmH2O) compared with control rats. In contrast, fast-twitch gastrocnemius arterioles of HLU rats demonstrated similar levels of spontaneous tone [6 ± 2% (HLU) vs. 6 ± 2% (control)] and myogenic reactivity to control rats. Neither KCl-induced contractile responses (10–50 mM KCl) nor VGCC density was significantly different between mixed gastrocnemius arterioles of HLU and control rats. These results suggest that HLU produces diverse adaptations in myogenic reactivity of arterioles isolated from different fiber-type regions of a single skeletal muscle. Furthermore, alterations in myogenic responses were not attributable to altered VGCC density.
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Davis, M. J. "Myogenic response gradient in an arteriolar network." American Journal of Physiology-Heart and Circulatory Physiology 264, no. 6 (June 1, 1993): H2168—H2179. http://dx.doi.org/10.1152/ajpheart.1993.264.6.h2168.
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Experiments were conducted to test the hypothesis that a longitudinal gradient in myogenic responsiveness exists within an arteriolar network. Single arterioles were dissected from the hamster cheek pouch, cannulated with micropipettes, and transferred to an inverted microscope for in vitro study. Pressure-diameter relationships of five branching orders of arterial vessels were measured in the presence of spontaneous vascular tone and after elimination of tone with a Ca(2+)-free solution containing nitroprusside. At luminal pressures matching those found in vivo, the diameters of the vessels with spontaneous tone were as follows: small arteries, 81 microns; first-order arterioles, 52 microns; second-order arterioles, 32 microns; third-order arterioles, 24 microns; and fourth-order arterioles, 11 microns. All branching orders of vessels exhibited true myogenic responses as indicated by negative slopes of their pressure-diameter relationships. Each vascular branching order exhibited its maximum myogenic responsiveness at a pressure near or just slightly higher than its normal pressure as measured in vivo. Relative myogenic responsiveness increased with decreasing vessel size down to the level of the second- and third-order arterioles, whereas fourth-order arterioles were substantially less responsive than third-order arterioles. A compilation of data from numerous in vivo and in vitro studies suggests that the same myogenic response pattern may be found in other vascular beds.
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Ungvari, Zoltan, and Akos Koller. "Selected Contribution: NO released to flow reduces myogenic tone of skeletal muscle arterioles by decreasing smooth muscle Ca2+sensitivity." Journal of Applied Physiology 91, no. 1 (July 1, 2001): 522–27. http://dx.doi.org/10.1152/jappl.2001.91.1.522.
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To clarify the contribution of intracellular Ca2+ concentration ([Ca2+]i)-dependent and -independent signaling mechanisms in arteriolar smooth muscle (aSM) to modulation of arteriolar myogenic tone by nitric oxide (NO), released in response to increases in intraluminal flow from the endothelium, changes in aSM [Ca2+]i and diameter of isolated rat gracilis muscle arterioles (pretreated with indomethacin) were studied by fluorescent videomicroscopy. At an intraluminal pressure of 80 mmHg, [Ca2+]i significantly increased and myogenic tone developed in response to elevations of extracellular Ca2+ concentration. The Ca2+ channel inhibitor nimodipine substantially decreased [Ca2+]i and completely inhibited myogenic tone. Dilations to intraluminal flow (that were inhibited by N ω-nitro-l-arginine methyl ester) or dilations to the NO donor S-nitroso- N-acetyl-dl-penicillamine (that were inhibited by the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one) were not accompanied by substantial decreases in aSM [Ca2+]i. 8-Bromoguanosine cGMP and the cGMP-specific phosphodiesterase inhibitor zaprinast significantly dilated arterioles yet elicited only minimal decreases in [Ca2+]i. Thus flow-induced endothelial release of NO elicits relaxation of arteriolar smooth muscle by a cGMP-dependent decrease of the Ca2+ sensitivity of the contractile apparatus without substantial changes in the pressure-induced level of [Ca2+]i.
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Brayden, Joseph E., Yao Li, and Matthew J. Tavares. "Purinergic Receptors Regulate Myogenic Tone in Cerebral Parenchymal Arterioles." Journal of Cerebral Blood Flow & Metabolism 33, no. 2 (November 21, 2012): 293–99. http://dx.doi.org/10.1038/jcbfm.2012.169.
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Myogenic tone is a fundamental aspect of vascular behavior in resistance arteries. This contractile response to changes in intravascular pressure is critically involved in blood flow autoregulation in tissues such as the brain, kidneys, and heart. Myogenic tone also helps regulate precapillary pressure and provides a level of background tone upon which vasodilator stimuli act to increase tissue perfusion when appropriate. Despite the importance of these processes in the brain, little is known about the mechanisms involved in control of myogenic tone in the cerebral microcirculation. Here, we report that pharmacological inhibition of P2Y4 and P2Y6 pyrimidine receptors nearly abolished myogenic tone in cerebral parenchymal arterioles (PAs). Molecular suppression of either P2Y4 or P2Y6 receptors using antisense oligodeoxynucleotides reduced myogenic tone by 44% ± 8% and 45% ± 7%, respectively. These results indicate that both receptor isoforms are activated by increased intravascular pressure, which enhances the activity of voltage-dependent calcium channels and increases myogenic tone in PAs. Enhancement or inhibition of ectonucleotidase activity had no effect on parenchymal arteriolar myogenic tone, indicating that this response is not mediated by local release of nucleotides, but rather may involve direct mechanical activation of P2Y receptors in the smooth muscle cells.
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Hill, Michael A., Gerald A. Meininger, Michael J. Davis, and Ismail Laher. "Therapeutic potential of pharmacologically targeting arteriolar myogenic tone." Trends in Pharmacological Sciences 30, no. 7 (July 2009): 363–74. http://dx.doi.org/10.1016/j.tips.2009.04.008.
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Jackson, William F., and Erika M. Boerman. "Regional heterogeneity in the mechanisms of myogenic tone in hamster arterioles." American Journal of Physiology-Heart and Circulatory Physiology 313, no. 3 (September 1, 2017): H667—H675. http://dx.doi.org/10.1152/ajpheart.00183.2017.
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Myogenic tone is an important feature of arterioles and resistance arteries, but the mechanisms responsible for this hallmark characteristic remain unclear. We used pharmacological inhibitors to compare the roles played by phospholipase C (PLC; 10 μM U73122), inositol 1,4,5-trisphosphate receptors (IP3Rs; 100 μM 2-aminoethoxydiphenylborane), protein kinase C (10 μM bisindolylmaleimide I), angiotensin II type 1 receptors (1 μM losartan), Rho kinase (10 nM−30 μM Y27632 or 300 nM H1152), stretch-activated ion channels (10 nM−1 μM Gd3+ or 5 μM spider venom toxin GsMTx-4) and L-type voltage-gated Ca2+ channels (0.3–100 μM diltiazem) in myogenic tone of cannulated, pressurized (80 cmH2O), second-order hamster cremaster or cheek pouch arterioles. Effective inhibition of either PLC or IP3Rs dilated cremaster arterioles, inhibited Ca2+ waves, and reduced global Ca2+ levels. In contrast, cheek pouch arterioles did not display Ca2+ waves and inhibition of PLC or IP3Rs had no effect on myogenic tone or intracellular Ca2+ levels. Inhibition of Rho kinase dilated both cheek pouch and cremaster arterioles with equal efficacy and potency but also reduced intracellular Ca2+ signals in both arterioles. Similarly, inhibition of mechanosensitive ion channels with Gd2+ or GsMTx-4 produced comparable dilation in both arterioles. Inhibition of L-type Ca2+ channels with diltiazem was more effective in dilating cremaster (86 ± 5% dilation, n = 4) than cheek pouch arterioles (54 ± 4% dilation, n = 6, P < 0.05). Thus, there are substantial differences in the mechanisms underlying myogenic tone in hamster cremaster and cheek pouch arterioles. Regional heterogeneity in myogenic mechanisms could provide new targets for drug development to improve regional blood flow in a tissue-specific manner. NEW & NOTEWORTHY Regional heterogeneity in the mechanisms of pressure-induced myogenic tone implies that resistance vessels may be able to alter myogenic signaling pathways to adapt to their environment. A better understanding of the spectrum of myogenic mechanisms could provide new targets to treat diseases that affect resistance artery and arteriolar function.
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Tykocki, Nathan R., Adrian D. Bonev, Thomas A. Longden, Thomas J. Heppner, and Mark T. Nelson. "Inhibition of vascular smooth muscle inward-rectifier K+ channels restores myogenic tone in mouse urinary bladder arterioles." American Journal of Physiology-Renal Physiology 312, no. 5 (May 1, 2017): F836—F847. http://dx.doi.org/10.1152/ajprenal.00682.2016.
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Prolonged decreases in urinary bladder blood flow are linked to overactive and underactive bladder pathologies. However, the mechanisms regulating bladder vascular reactivity are largely unknown. To investigate these mechanisms, we examined myogenic and vasoactive properties of mouse bladder feed arterioles (BFAs). Unlike similar-sized arterioles from other vascular beds, BFAs failed to constrict in response to increases in intraluminal pressure (5–80 mmHg). Consistent with this lack of myogenic tone, arteriolar smooth muscle cell membrane potential was hyperpolarized (−72.8 ± 1.4 mV) at 20 mmHg and unaffected by increasing pressure to 80 mmHg (−74.3 ± 2.2 mV). In contrast, BFAs constricted to the thromboxane analog U-46619 (100 nM), the adrenergic agonist phenylephrine (10 µM), and KCl (60 mM). Inhibition of nitric oxide synthase or intermediate- and small-conductance Ca2+-activated K+ channels did not alter arteriolar diameter, indicating that the dilated state of BFAs is not attributable to overactive endothelium-dependent dilatory influences. Myocytes isolated from BFAs exhibited BaCl2 (100 µM)-sensitive K+ currents consistent with strong inward-rectifier K+ (KIR) channels. Notably, block of these KIR channels “restored” pressure-induced constriction and membrane depolarization. This suggests that these channels, in part, account for hyperpolarization and associated absence of tone in BFAs. Furthermore, smooth muscle-specific knockout of KIR2.1 caused significant myogenic tone to develop at physiological pressures. This suggests that 1) the regulation of vascular tone in the bladder is independent of pressure, insofar as pressure-induced depolarizing conductances cannot overcome KIR2.1-mediated hyperpolarization; and 2) maintenance of bladder blood flow during bladder filling is likely controlled by neurohumoral influences.
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Huang, An, and Akos Koller. "Endothelin and Prostaglandin H2Enhance Arteriolar Myogenic Tone in Hypertension." Hypertension 30, no. 5 (November 1997): 1210–15. http://dx.doi.org/10.1161/01.hyp.30.5.1210.
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Hill, M. A., M. J. Davis, and G. A. Meininger. "Cyclooxygenase inhibition potentiates myogenic activity in skeletal muscle arterioles." American Journal of Physiology-Heart and Circulatory Physiology 258, no. 1 (January 1, 1990): H127—H133. http://dx.doi.org/10.1152/ajpheart.1990.258.1.h127.
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The proposition that arteriolar constriction to increased intravascular pressure is mediated through either the increased local production of an eicosanoid constrictor factor or decreased production of a dilating factor was examined. The myogenic response of arterioles was studied by enclosing anesthetized rats in an airtight Plexiglas box with the cremaster muscle exteriorized into a tissue bath containing Krebs solution. Microvascular responses were observed by video microscopy. The arteriolar response to a 20-mmHg increase in intravascular pressure was examined in the absence or presence of cyclooxygenase inhibition. In the absence of cyclooxygenase inhibition, second-order arterioles (2As) responded passively to increased pressure by distending to 107 +/- 1% of control diameter. In the presence of the indomethacin, 2As constricted to 79 +/- 5% of control. Third-order arterioles (3As) constricted to 47 +/- 8% of control without indomethacin and similarly to 33 +/- 4% with indomethacin. To test whether inhibitors of endothelium-derived relaxation factor would potentiate the myogenic response of 3As, methylene blue or gossypol was topically applied to the cremaster muscle. Neither inhibitor was found to augment the myogenic vasoconstriction; however, these inhibitors were observed to significantly reduce basal vascular tone. In comparison, the tonic local production of dilating prostaglandins appears to attenuate myogenic activity as demonstrated by the appearance of myogenic activity in the normally passive 2As when exposed to cyclooxygenase inhibitors.
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Massett, Michael P., Zoltan Ungvari, Anna Csiszar, Gabor Kaley, and Akos Koller. "Different roles of PKC and MAP kinases in arteriolar constrictions to pressure and agonists." American Journal of Physiology-Heart and Circulatory Physiology 283, no. 6 (December 1, 2002): H2282—H2287. http://dx.doi.org/10.1152/ajpheart.00544.2002.
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Protein kinase C (PKC) and mitogen-activated protein (MAP) kinases have been implicated in the modulation of agonist-induced contractions of large vessels. However, their role in pressure- and agonist-induced constrictions of skeletal muscle arterioles, which have a major role in regulating peripheral resistance, is not clearly elucidated. Thus constrictions of isolated rat gracilis muscle arterioles (∼80 μm in diameter) to increases in intraluminal pressure and to norepinephrine (NE) or angiotensin II (ANG II) were assessed in the absence or presence of chelerythrine, PD-98058, and SB-203580 (inhibitors of PKC, p42/44 and p38 MAP kinase pathways, respectively). Arteriolar constriction to NE and ANG II were significantly reduced by chelerythrine (by ∼90%) and unaffected by SB-203580, whereas PD-98058 decreased only ANG II-induced constrictions (by ∼60%). Pressure-induced increases in wall tension (from 0.1 to 0.7 N/m) resulted in significant arteriolar constrictions (50% maximum) that were abolished by chelerythrine without altering smooth muscle intracellular Ca2+ concentration ([Ca2+]i) (fura 2 microfluorimetry). PD-98058 and SB-203580 significantly decreased the magnitude of myogenic tone (by 20% and 60%, respectively) and reduced the sensitivity of the myogenic mechanism to wall tension, causing a significant rightward shift in the wall tension-myogenic tone relationship without affecting smooth muscle [Ca2+ i]. MAP kinases were demonstrated with Western blotting. Thus in skeletal muscle arterioles 1) PKC is involved in both myogenic and agonist-induced constrictions , 2) PD-98058-sensitive p42/44 MAP kinases modulate both wall tension-dependent and ANG II-induced constrictions, whereas 3) a SB-203580-sensitive p38 MAP kinase pathway seems to be specifically involved in the mechanotransduction of wall tension.
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Falcone, J. C., M. J. Davis, and G. A. Meininger. "Endothelial independence of myogenic response in isolated skeletal muscle arterioles." American Journal of Physiology-Heart and Circulatory Physiology 260, no. 1 (January 1, 1991): H130—H135. http://dx.doi.org/10.1152/ajpheart.1991.260.1.h130.
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The goal of this study was to determine whether the endothelium played a role in the myogenic response of skeletal muscle arterioles. First-order arterioles (n = 15) were isolated from the rat cremaster muscle and cannulated for in vitro study. The development of spontaneous tone reduced the diameter of the isolated arterioles from 166.7 +/- 7.6 microns to 89.2 +/- 7.2 microns. The arterioles were exposed to step changes in intraluminal pressure over a range of 10–170 cmH2O and had no flow through their lumen. The vessels exhibited active constriction to step increases or active dilation to step decreases in pressure (50–150 cmH2O). At 90 cmH2O, arterioles dilated by 89.2 +/- 6.0% in response to the endothelium-dependent vasodilator acetylcholine (10(-6) M; ACh) and 89.6 +/- 10.9% in response to endothelium-independent dilator adenosine (10(-4) M; Ado). The endothelium was physically denuded by rubbing the vessel lumen. After denudation, the arteriolar dilation to ACh was abolished, whereas the dilation to Ado was unaltered. The absence of endothelium was verified by electron microscopy. Basal tone and the response to changes in pressure were not significantly different from endothelium-intact vessels. These studies indicate that the endothelium is not responsible for myogenic activity or development of spontaneous tone in skeletal muscle arterioles.
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Liu, J., M. A. Hill, and G. A. Meininger. "Mechanisms of myogenic enhancement by norepinephrine." American Journal of Physiology-Heart and Circulatory Physiology 266, no. 2 (February 1, 1994): H440—H446. http://dx.doi.org/10.1152/ajpheart.1994.266.2.h440.
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Mechanisms contributing to the ability of norepinephrine (NE) to enhance arteriolar myogenic responsiveness were studied in the rat cremaster muscle. Anesthetized rats were enclosed in an airtight box that could be pressurized to increase intravascular pressure in the cremaster, which was exteriorized into a tissue bath. Vessel diameter, intravascular pressure, and red cell velocity were measured in the first-order (1A) arteriole during box pressure increases of 10, 20, and 30 mmHg. Control arterioles [diameter = 113 +/- 3 (SE) microns] did not exhibit myogenic constriction in response to step increases in intravascular pressure (e.g., + 30 mmHg, diameter = 122 +/- 5 microns), whereas after 25% constriction with NE (diameter = 85 +/- 2 microns) arterioles exhibited significant myogenic constriction (e.g., +30 mmHg, diameter = 70 +/- 4 microns). The NE effect on myogenic reactivity was augmented by Ca2+ channel agonists and inhibited by antagonists, suggesting a role for voltage-operated Ca2+ channels. In contrast to NE, exposure to KCl (30 mM) did not enhance myogenic responsiveness, suggesting that factors in addition to voltage-operated channels were involved in the NE effect. The protein kinase C (PKC) activator indolactam (1 microM) was found to increase vascular tone in the 1A arterioles (diameter = 109 +/- 6 to 89 +/- 7 microns) and to induce significant myogenic responsiveness similar to that produced by NE (e.g., +30 mmHg, diameter = 65 +/- 9 microns). Staurosporine (0.1 microM) and calphostin C (1 microM), inhibitors of PKC, significantly attenuated the NE-induced myogenic response.(ABSTRACT TRUNCATED AT 250 WORDS)
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Frisbee, Jefferson C., John M. Hollander, Robert W. Brock, Han-Gang Yu, and Matthew A. Boegehold. "Integration of skeletal muscle resistance arteriolar reactivity for perfusion responses in the metabolic syndrome." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 296, no. 6 (June 2009): R1771—R1782. http://dx.doi.org/10.1152/ajpregu.00096.2009.
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Previous study suggests that with evolution of the metabolic syndrome, patterns of arteriolar reactivity are profoundly altered and may constrain functional hyperemia. This study investigated interactions between parameters of vascular reactivity at two levels of resistance arterioles in obese Zucker rats (OZR), translating these observations into perfusion regulation for in situ skeletal muscle. Dilation of isolated and in situ resistance arterioles from OZR to acetylcholine, arachidonic acid (AA), and hypoxia (isolated arterioles only) were blunted vs. lean Zucker rats (LZR), although dilation to adenosine was intact. Increased adrenergic tone (phenylephrine) or intralumenal pressure (ILP) impaired dilation in both strains (OZR>LZR). Treatment of OZR arterioles with Tempol (superoxide dismutase mimetic) or SQ-29548 (prostaglandin H2/thromboxane A2 receptor antagonist) improved dilator reactivity under control conditions and with increased ILP, but had minimal effect with increased adrenergic tone. Arteriolar dilation to adenosine was well maintained in both strains under all conditions. For in situ cremasteric arterioles, muscle contraction-induced elevations in metabolic demand elicited arteriolar dilations and hyperemic responses that were blunted in OZR vs. LZR, although distal parallel arterioles were characterized by heterogeneous dilator and perfusion responses. α-Adrenoreceptor blockade improved outcomes at rest but had minimal effect with elevated metabolic demand. Treatment with Tempol or SQ-29548 had minimal impact at rest, but lessened distal arteriolar perfusion heterogeneity with increased metabolic demand. In blood-perfused gastrocnemius of OZR, perfusion was constrained primarily by adrenergic tone, while myogenic activation and endothelium-dependent dilation did not appear to contribute significantly to ischemia. These results of this novel, integrated approach suggest that adrenergic tone and metabolic dilation are robust determinants of bulk perfusion to skeletal muscle of OZR, while endothelial dysfunction may more strongly regulate perfusion distribution homogeneity via the impact of oxidant stress and AA metabolism.
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Weihprecht, H., J. N. Lorenz, J. P. Briggs, and J. Schnermann. "Vasoconstrictor effect of angiotensin and vasopressin in isolated rabbit afferent arterioles." American Journal of Physiology-Renal Physiology 261, no. 2 (August 1, 1991): F273—F282. http://dx.doi.org/10.1152/ajprenal.1991.261.2.f273.
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The present studies were performed to examine the vasoconstrictor effect of angiotensin II (ANG II), angiotensin III (ANG III), and vasopressin in isolated afferent arterioles of the rabbit kidney. Afferent arterioles were dissected together with their glomerulus and perfused with a pressure head of 120 cmH2O. Changes in vasomotor tone were assessed as diameter changes on videotaped recordings. Afferent arterioles responded to the angiotensins and vasopressin with dose-dependent reductions in vascular diameters with half-maximum responses being observed at concentrations between 10(-9) and 10(-8) M. Responses to ANG II and III were inhibited by saralasin. Contractile responses to ANG II and vasopressin were not altered by prior occlusion of the efferent arteriole, suggesting that afferent vasoconstriction does not represent a myogenic reaction to an increase in efferent resistance. The vasoconstrictor response to ANG II was largely eliminated by removal of the glomerulus and the distal-most portion of the afferent arteriole, whereas the response to vasopressin remained intact. Our data are consistent with the notion that the juxtaglomerular apparatus (JGA) and/or glomerulus may control proximal afferent arteriolar contractility by electrotonic or myogenic coupling mechanisms or by producing cofactors that modulate vasomotor responses.
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Murphy, Timothy V., Brian E. Spurrell, and Michael A. Hill. "Tyrosine phosphorylation following alterations in arteriolar intraluminal pressure and wall tension." American Journal of Physiology-Heart and Circulatory Physiology 281, no. 3 (September 1, 2001): H1047—H1056. http://dx.doi.org/10.1152/ajpheart.2001.281.3.h1047.
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Arterioles respond to increased transmural pressure with myogenic constriction. The present study investigated the role of tyrosine phosphorylation in myogenic activity. Cannulated segments of a rat cremaster arteriole were fixed under pressure, followed by incubation with fluorescein isothiocyanate (FITC)-conjugated anti-phosphotyrosine. Smooth muscle cell fluorescence intensity was measured with the use of confocal laser-scanning microscopy. Anti-phosphotyrosine fluorescence intensity in muscle cells of arterioles maintained at 100 mmHg was reduced by the tyrosine kinase inhibitor tyrphostin A47 (30 μM) and increased by the tyrosine phosphatase inhibitor pervanadate (100 μM). In time-course experiments, anti-phosphotyrosine fluorescence increased slowly (over 5 min) after an acute increase in intraluminal pressure, and was dissociated from myogenic contraction (within 1 min). In contrast, angiotensin II (0.1 μM) caused rapid constriction and increased tyrosine phosphorylation. Anti-phosphotyrosine fluorescence was also pressure dependent (10–100 mmHg). Abolition of myogenic activity, either through removal of extracellular Ca2+, or exposure to verapamil (5 μM) or forskolin (0.1 μM) caused a further increase in anti-phosphotyrosine fluorescence. We conclude that transmural pressure and/or wall tension in arterioles causes increased tyrosine phosphorylation; however, this is not involved in the acute phase of myogenic constriction but may be involved in later responses, such as sustained myogenic tone or mechanisms possibly related to growth.
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Westcott, Erika B., and William F. Jackson. "Heterogeneous function of ryanodine receptors, but not IP3 receptors, in hamster cremaster muscle feed arteries and arterioles." American Journal of Physiology-Heart and Circulatory Physiology 300, no. 5 (May 2011): H1616—H1630. http://dx.doi.org/10.1152/ajpheart.00728.2010.
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The roles played by ryanodine receptors (RyRs) and inositol 1,4,5-trisphosphate receptors (IP3Rs) in vascular smooth muscle in the microcirculation remain unclear. Therefore, the function of both RyRs and IP3Rs in Ca2+ signals and myogenic tone in hamster cremaster muscle feed arteries and downstream arterioles were assessed using confocal imaging and pressure myography. Feed artery vascular smooth muscle displayed Ca2+ sparks and Ca2+ waves, which were inhibited by the RyR antagonists ryanodine (10 μM) or tetracaine (100 μM). Despite the inhibition of sparks and waves, ryanodine or tetracaine increased global intracellular Ca2+ and constricted the arteries. The blockade of IP3Rs with xestospongin D (5 μM) or 2-aminoethoxydiphenyl borate (100 μM) or the inhibition of phospholipase C using U-73122 (10 μM) also attenuated Ca2+ waves without affecting Ca2+ sparks. Importantly, the IP3Rs and phospholipase C antagonists decreased global intracellular Ca2+ and dilated the arteries. In contrast, cremaster arterioles displayed only Ca2+ waves: Ca2+ sparks were not observed, and neither ryanodine (10–50 μM) nor tetracaine (100 μM) affected either Ca2+ signals or arteriolar tone despite the presence of functional RyRs as assessed by responses to the RyR agonist caffeine (10 mM). As in feed arteries, arteriolar Ca2+ waves were attenuated by xestospongin D (5 μM), 2-aminoethoxydiphenyl borate (100 μM), and U-73122 (10 μM), accompanied by decreased global intracellular Ca2+ and vasodilation. These findings highlight the contrasting roles played by RyRs and IP3Rs in Ca2+ signals and myogenic tone in feed arteries and demonstrate important differences in the function of RyRs between feed arteries and downstream arterioles.
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Kuo, L., M. J. Davis, and W. M. Chilian. "Myogenic activity in isolated subepicardial and subendocardial coronary arterioles." American Journal of Physiology-Heart and Circulatory Physiology 255, no. 6 (December 1, 1988): H1558—H1562. http://dx.doi.org/10.1152/ajpheart.1988.255.6.h1558.
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The goal of this study was to examine myogenic responses of isolated porcine subepicardial and subendocardial arterioles (80–100 micron in diameter) within physiological ranges of intraluminal pressure. Arterioles were located by perfusion with india ink-gelatin solution then dissected and cannulated with glass micropipettes. Intraluminal pressure was altered in 20-cmH2O steps over the range of 20–140 cmH2O. IN physiological salt solution (36–37 degrees C), the coronary arterioles developed spontaneous tone and exhibited myogenic responses. At the lower pressures (20–60 cmH2O), subendocardial arterioles responded passively (diameter decreased from a control diameter at 60 cmH2O), whereas subepicardial arterioles maintained their diameters. At higher pressures (100–140 cmH2O), both subepicardial and subendocardial arterioles demonstrated myogenic constriction, but subepicardial arterioles demonstrated greater myogenic constriction than subendocardial arterioles. This implies that myogenic autoregulation in subepicardial arterioles is better than that in the subendocardial arterioles at both low and high pressures. In the presence of nitroprusside (10(-4) M), all arterioles responded to pressure changes passively, and there were no differences between subepicardial and subendocardial vessels. The functional integrity of the endothelium was verified by relaxation to substance P (10(-7) M). This is the first in vitro study to demonstrate coronary myogenic activity and transmural differences in these arteriolar responses. Our data support the concept that myogenic mechanisms in 80 to 100-micron arterioles may actively contribute to autoregulation of coronary blood flow.
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Jackson, P. A., and B. R. Duling. "Myogenic response and wall mechanics of arterioles." American Journal of Physiology-Heart and Circulatory Physiology 257, no. 4 (October 1, 1989): H1147—H1155. http://dx.doi.org/10.1152/ajpheart.1989.257.4.h1147.
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The magnitude of the arteriolar response to altered intraluminal pressure was assessed in isolated, cannulated vessels of the hamster cheek pouch. Microvessels were studied during various levels of smooth muscle activation, either occurring spontaneously, or resulting from the application of exogenous agonists including potassium (35 or 70 mM) and phenylephrine (1.25 or 2.50 x 10(-6) M). Diameter-pressure curves were obtained by lowering intraluminal pressure from 60 to 0 mmHg in seven steps at 3-min intervals. At an intraluminal pressure of 40 mmHg, spontaneous tone produced an average constriction to 34 +/- 2% of the maximum diameter. Step reductions in pressure typically led to reductions in the level of activation of the muscle, which resulted in a net dilation over a significant pressure range. This “myogenic response” was more effective in modifying spontaneous tone than in modifying exogenous tone. In fact, the data suggest that reduction of the intraluminal pressure to zero can result in complete inactivation of spontaneous tone. Complete inactivation was not observed when contractions were induced by exogenous agonists, however. The magnitude of the myogenic response in arterioles was consistent with a role in autoregulation, which is 2.5-fold greater than that previously reported for small arteries. The data demonstrate that in the analysis of the mechanics of submaximally activated blood vessels one must include considerations of two phenomenon: the classical stress-length behavior as determined under conditions of maximal activation, and a superimposed modification of the activation level induced by stress- or length-dependent processes. Furthermore, the findings indicate substantial differences in response when tone is spontaneous compared with the case when tone is induced by exogenous agonists.
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Kauffenstein, Gilles, Sophie Tamareille, Fabrice Prunier, Charlotte Roy, Audrey Ayer, Bertrand Toutain, Marie Billaud, et al. "Central Role of P2Y 6 UDP Receptor in Arteriolar Myogenic Tone." Arteriosclerosis, Thrombosis, and Vascular Biology 36, no. 8 (August 2016): 1598–606. http://dx.doi.org/10.1161/atvbaha.116.307739.
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Williamson, Geoffrey A., Rodger Loutzenhiser, Xuemei Wang, Karen Griffin, and Anil K. Bidani. "Systolic and mean blood pressures and afferent arteriolar myogenic response dynamics: a modeling approach." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 295, no. 5 (November 2008): R1502—R1511. http://dx.doi.org/10.1152/ajpregu.00490.2007.
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The afferent arteriolar myogenic response contributes to the autoregulation of renal blood flow (RBF) and glomerular filtration rate (GFR), and plays an essential role in protecting the kidney against hypertensive injury. Systolic blood pressure (SBP) is most closely linked to renal injury, and a myogenic response coupled to this signal would facilitate renal protection, whereas mean blood pressure (MBP) influences RBF and GFR. The relative role of SBP vs. MBP as the primary determinant of myogenic tone is an area of current controversy. Here, we describe two mathematical models, Model-Avg and Model-Sys, that replicate the different delays and time constants of vasoconstrictor and vasodilator phases of the myogenic responses of the afferent arteriole. When oscillating pressures are applied, the MBP determines the magnitude of the myogenic response of Model-Avg, and the SBP determines the response of Model-Sys. Simulations evaluating the responses of both models to square-wave pressure oscillations and to narrow pressure pulses show decidedly better agreement between Model-Sys and afferent arteriolar responses observed in cortical nephrons in the in vitro hydronephrotic kidney model. Analysis showing that the difference in delay times of the vasoconstrictor and vasodilator phases determines the frequency range over which SBP triggers Model-Sys's response was confirmed with simulations using authentic blood pressure waveforms. These observations support the postulate that SBP is the primary determinant of the afferent arteriole's myogenic response and indicate that differences in the delays in initiation vs. termination of the response, rather than in time constants, are integral to this phenomenon.
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Huang, A., D. Sun, A. Koller, and G. Kaley. "Gender difference in myogenic tone of rat arterioles is due to estrogen-induced, enhanced release of NO." American Journal of Physiology-Heart and Circulatory Physiology 272, no. 4 (April 1, 1997): H1804—H1809. http://dx.doi.org/10.1152/ajpheart.1997.272.4.h1804.
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The characteristics of arteriolar myogenic responses of female rats have not been investigated. Thus experiments were conducted on isolated gracilis muscle arterioles (approximately 55 microm diameter) of four groups of 12-wk-old rats: male rats, female rats, ovariectomized female rats with no estrogen replacement (OV), and ovariectomized female rats with estrogen replacement (OV + E2, 50 microg/kg s.c. injection of 17beta-estradiol benzoate every 48 h). Diameter changes in response to increases in perfusion pressure from 20 to 140 mmHg and to various concentrations of substance P (SP, 10(-9)-5 x 10(-8) M) and sodium nitroprusside (SNP, 10(-8)-10(-6) M) were measured before and after administration of N(omega)-nitro-L-arginine (L-NNA, 10(-4) M), an inhibitor of NO synthase. Arteriolar diameters of male and OV female rats were significantly less at 60-140 mmHg pressure than those of normal female and OV + E2 female rats (at 80 mmHg, 45.4 +/- 1.8 and 43.1 +/- 2.2 vs. 58.4 +/- 1.6 and 57.3 +/- 1.3%). L-NNA elicited a significantly greater downward shift of pressure-diameter curves in arterioles of normal female and OV + E2 female rats than in arterioles of male and OV female rats (28.6 +/- 4.6 and 30.6 +/- 4.7 vs. 13.2 +/- 0.9 and 10.4 +/- 2.6%). Dilations of arterioles from normal female and OV +/- E2 female rats to SP were significantly greater (by 50-60%) than those from male and OV female rats (20.8 +/- 1.8 and 22.3 +/- 1.9 vs. 13.8 +/- 1.4 and 13.8 +/- 0.6% at 10(-8) M). L-NNA did not affect dilations to SNP but significantly reduced the dilation of arterioles in all groups to SP, more so in arterioles of male and OV female rats than in arterioles of the other two groups. We conclude that pressure-induced myogenic constriction of arterioles of female rats is less pronounced than that of male rats; this is, most likely, due to the enhanced release and/or activity of NO related to the presence of estrogen.
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Arciero, Julia C., Brian E. Carlson, and Timothy W. Secomb. "Theoretical model of metabolic blood flow regulation: roles of ATP release by red blood cells and conducted responses." American Journal of Physiology-Heart and Circulatory Physiology 295, no. 4 (October 2008): H1562—H1571. http://dx.doi.org/10.1152/ajpheart.00261.2008.
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A proposed mechanism for metabolic flow regulation involves the saturation-dependent release of ATP by red blood cells, which triggers an upstream conducted response signal and arteriolar vasodilation. To analyze this mechanism, a theoretical model is used to simulate the variation of oxygen and ATP levels along a flow pathway of seven representative segments, including two vasoactive arteriolar segments. The conducted response signal is defined by integrating the ATP concentration along the vascular pathway, assuming exponential decay of the signal in the upstream direction with a length constant of ∼1 cm. Arteriolar tone depends on the conducted metabolic signal and on local wall shear stress and wall tension. Arteriolar diameters are calculated based on vascular smooth muscle mechanics. The model predicts that conducted responses stimulated by ATP release in venules and propagated to arterioles can account for increases in perfusion in response to increased oxygen demand that are consistent with experimental findings at low to moderate oxygen consumption rates. Myogenic and shear-dependent responses are found to act in opposition to this mechanism of metabolic flow regulation.
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Hill, Michael A., Hui Zou, Simon J. Potocnik, Gerald A. Meininger, and Michael J. Davis. "Invited Review: Arteriolar smooth muscle mechanotransduction: Ca2+ signaling pathways underlying myogenic reactivity." Journal of Applied Physiology 91, no. 2 (August 1, 2001): 973–83. http://dx.doi.org/10.1152/jappl.2001.91.2.973.
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The smooth muscle of arterioles responds to an increase in intraluminal pressure with vasoconstriction and with vasodilation when pressure is decreased. Such myogenic vasoconstriction provides a level of basal tone that enables arterioles to appropriately adjust diameter in response to neurohumoral stimuli. Key in this process of mechanotransduction is the role of changes in intracellular Ca2+. However, it is becoming clear that considerable complexity exists in the spatiotemporal characteristics of the Ca2+ signal and that changes in intracellular Ca2+ may play roles other than direct effects on the contractile process via activation of myosin light-chain phosphorylation. The involvement of Ca2+ may extend to modulation of ion channels and release of Ca2+ from the sarcoplasmic reticulum, alterations in Ca2+ sensitivity, and coupling between cells within the vessel wall. The purpose of this brief review is to summarize the current literature relating to Ca2+ and the arteriolar myogenic response. Consideration is given to coupling of Ca2+ changes to the mechanical stimuli, sources of Ca2+, involvement of ion channels, and spatiotemporal aspects of intracellular Ca2+ signaling.
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Meininger, G. A., D. C. Zawieja, J. C. Falcone, M. A. Hill, and J. P. Davey. "Calcium measurement in isolated arterioles during myogenic and agonist stimulation." American Journal of Physiology-Heart and Circulatory Physiology 261, no. 3 (September 1, 1991): H950—H959. http://dx.doi.org/10.1152/ajpheart.1991.261.3.h950.
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Vascular smooth muscle calcium was measured during agonist treatment or pressure-induced stimulation of the myogenic response in isolated first-order skeletal muscle arterioles. Arterioles (40-180 microns) with spontaneous tone were isolated from rat cremaster muscle and cannulated. Arterioles were loaded with the calcium-sensitive dye fura-2 and excited at 340 and 380 nm. Images of vessel fluorescence were formed with a fluorescence microscope and digitized using an image processor coupled to a low light level camera. The fluorescent images allowed individual vascular smooth muscle cells to be seen within the arteriolar wall. Fluorescent intensity of the vessel wall, expressed as the ratio of fluorescence at 340 nm/380 nm, was used to estimate changes in vessel wall calcium. Topical application of norepinephrine (10 microM) to the arterioles caused a rapid and sustained constriction of the arterioles (64% of basal diam). The calcium response was biphasic consisting of a transient spike to 271% of basal followed by a decrease to a new steady state at 143% of basal. In comparison, steady-state indolactam (1 microM) produced a similar degree of constriction without an increase in calcium. Adenosine significantly dilated (35%) the arterioles and produced a decrease (24%) in vessel wall calcium. To investigate the myogenic response, intravascular pressure was step increased from 90 to 130 cmH2O. Increasing intravascular pressure caused an initial increase in vessel diameter of approximately 5% followed by active constriction that returned diameter to basal diameter. In association with this diameter change, estimated vessel wall calcium increased rapidly 8 +/- 2% and then continued to increase more slowly and remained elevated at 10-15% above basal levels. This study demonstrates the successful application of calcium-imaging technology in isolated arterioles for study of the role of calcium in arteriolar function. Results indicate that the calcium-contraction relationship differs for different agonists and are further consistent with a role for pressure-induced increases in vascular smooth muscle calcium during the myogenic response.
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Heaps, Cristine L., Mildred L. Mattox, Katherine A. Kelly, Cynthia J. Meininger, and Janet L. Parker. "Exercise training increases basal tone in arterioles distal to chronic coronary occlusion." American Journal of Physiology-Heart and Circulatory Physiology 290, no. 3 (March 2006): H1128—H1135. http://dx.doi.org/10.1152/ajpheart.00973.2005.
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Endurance exercise training increases basal active tone in coronary arteries and enhances myogenic tone in coronary arterioles of control animals. Paradoxically, exercise training has also been shown to augment nitric oxide production and nitric oxide-mediated relaxation in coronary arterioles. The purpose of the present study was to examine the effect of exercise training on basal active tone of arterioles (∼150 μm ID) isolated from the collateral-dependent region of hearts exposed to chronic coronary occlusion. Ameroid occluders were surgically placed around the proximal left circumflex coronary artery of miniature swine. Arterioles were isolated from both the collateral-dependent and nonoccluded myocardial regions of sedentary (pen confined) and exercise-trained (treadmill run; 14 wk) pigs. Coronary tone was studied in isolated arterioles using microvessel myographs and standard isometric techniques. Exposure to nominally Ca2+-free external solution reduced resting tension in all arterioles; decreases were most profound ( P < 0.05) in arterioles from the collateral-dependent region of exercise-trained animals. Furthermore, nitric oxide synthase (NOS) inhibition ( Nω-nitro-l-arginine methyl ester; 100 μM) unmasked markedly increased nitric oxide-sensitive tone in arterioles from the collateral-dependent region of exercise-trained swine. Blockade of K+ channels revealed significantly enhanced K+ channel contribution to basal tone in collateral-dependent arterioles of exercise-trained pigs. Protein content of endothelial NOS (eNOS) and phosphorylated eNOS (pS1179), determined by immunoblot, was elevated in arterioles from exercise-trained animals with the greatest effect in collateral-dependent vasculature. Taken together, we demonstrate the interaction of opposing exercise training-enhanced arteriolar basal active tone, nitric oxide production, and K+ channel activity in chronic coronary occlusion, potentially enhancing the capacity to regulate blood flow to collateral-dependent myocardium.
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Hill, Michael A., Hui Zou, Michael J. Davis, Simon J. Potocnik, and Simone Price. "Transient increases in diameter and [Ca2+]i are not obligatory for myogenic constriction." American Journal of Physiology-Heart and Circulatory Physiology 278, no. 2 (February 1, 2000): H345—H352. http://dx.doi.org/10.1152/ajpheart.2000.278.2.h345.
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Studies were performed to determine the significance of temporal variation in vascular smooth muscle Ca2+ signaling during acute arteriolar myogenic constriction and, in particular, the importance of the stretch-induced intracellular Ca2+concentration ([Ca2+]i) transient in attaining a steady-state mechanical response. Rat cremaster arterioles (diameter ∼100 μm) were dissected from surrounding tissues, and vessel segments were pressurized in the absence of intraluminal flow. For [Ca2+]imeasurements, vessels were loaded with fura 2 and fluorescence emitted by excitation at 340 and 380 nm was measured using video-based image analysis. Ca2+ and diameter responses were examined after increases in intravascular pressure were applied as an acute step increase or a ramp function. Additional studies examined the effect of longitudinal vessel stretch on [Ca2+]i and arteriolar diameter. Step increase in intraluminal pressure (from 50 to 120 mmHg) caused biphasic change in [Ca2+]i and diameter. [Ca2+]i transiently increased to 114.0 ± 2.0% of basal levels and subsequently declined to 106.7 ± 4.4% at steady state. Diameter initially distended to 125.4 ± 2.1% of basal levels before constricting to 71.1 ± 1.2%. In contrast, when the same pressure increase was applied as a ramp function (over 5 min) transient vessel distension and transient increase in [Ca2+]i were prevented, yet at steady state vessels constricted to 71.3 ± 2.5%. Longitudinal stretch resulted in a large [Ca2+]i transient (158 ± 19% of basal) that returned to baseline despite maintenance of the stretch stimulus. The data demonstrate that the initial vessel distension (reflecting myocyte stretch) and associated global [Ca2+]i transient are not obligatory for myogenic contraction. Thus, although arteriolar smooth muscle cells are responsive to acute stretch, the resulting changes in myogenic tone may be more closely related to other mechanical variables such as wall tension.
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Zou, H., P. H. Ratz, and M. A. Hill. "Role of myosin phosphorylation and [Ca2+]i in myogenic reactivity and arteriolar tone." American Journal of Physiology-Heart and Circulatory Physiology 269, no. 5 (November 1, 1995): H1590—H1596. http://dx.doi.org/10.1152/ajpheart.1995.269.5.h1590.
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The aim of this study was to define the relationship between intraluminal pressure, intracellular calcium concentration ([Ca2+]i), and myosin light-chain (MLC) phosphorylation in isolated arterioles exhibiting myogenic tone. Cremaster muscles were removed from anesthetized rats, and arterioles (approximately 100-microns diam) were dissected from surrounding tissues and cannulated on glass pipettes. Vessels were warmed to 34 degrees C and initially pressurized to 70 mmHg in the absence of intraluminal flow. For [Ca2+]i measurements, vessels were loaded with 5 microM fura 2, and fluorescence emitted by excitation at 340 and 380 nm was measured. Data were considered in terms of changes in the fluorescence ratio (340/380 nm) and collected at steady-state intraluminal pressures between 30 and 170 mmHg. For measurement of MLC phosphorylation, vessels were frozen in acetone-dry ice followed by sonication in homogenizing buffer. Homogenates were separated by two-dimensional gel electrophoresis, and proteins were visualized by silver staining. MLC phosphorylation was quantitated photodensitometrically, and results are expressed as percent total 20-kDa MLC. Increasing intraluminal pressure resultedin significant constriction with increased [Ca2+]i and MLC phosphorylation. For example, the fluorescence ratio was 0.80 +/- 0.04 at 30 mmHg compared with 1.02 +/- 0.05 at 120 mmHg (n = 7 vessels); corresponding MLC-phosphorylation values were 27.7 +/- 1.6 and 39.6 +/- 3.0% (n = 6). MLC phosphorylation in arterioles superfused with 0 mM Ca(2+)-2 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) was 8.5 +/- 0.7%.(ABSTRACT TRUNCATED AT 250 WORDS)
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Clifford, Philip S., Brian S. Ferguson, Jeffrey L. Jasperse, and Michael A. Hill. "Arteriolar vasodilation involves actin depolymerization." American Journal of Physiology-Heart and Circulatory Physiology 315, no. 2 (August 1, 2018): H423—H428. http://dx.doi.org/10.1152/ajpheart.00723.2017.
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It is generally assumed that relaxation of arteriolar vascular smooth muscle occurs through hyperpolarization of the cell membrane, reduction in intracellular Ca2+ concentration, and activation of myosin light chain phosphatase/inactivation of myosin light chain kinase. We hypothesized that vasodilation is related to depolymerization of F-actin. Cremaster muscles were dissected in rats under pentobarbital sodium anesthesia (50 mg/kg). First-order arterioles were dissected, cannulated on glass micropipettes, pressurized, and warmed to 34°C. Internal diameter was monitored with an electronic video caliper. The concentration of G-actin was determined in flash-frozen intact segments of arterioles by ultracentrifugation and Western blot analyses. Arterioles dilated by ~40% of initial diameter in response to pinacidil (1 × 10−6 mM) and sodium nitroprusside (5 × 10−5 mM). The G-actin-to-smooth muscle 22α ratio was 0.67 ± 0.09 in arterioles with myogenic tone and increased significantly to 1.32 ± 0.34 ( P < 0.01) when arterioles were dilated with pinacidil and 1.14 ± 0.18 ( P < 0.01) with sodium nitroprusside, indicating actin depolymerization. Compared with control vessels (49 ± 5%), the percentage of phosphorylated myosin light chain was significantly reduced by pinacidil (24 ± 2%, P < 0.01) but not sodium nitroprusside (42 ± 4%). These findings suggest that actin depolymerization is an important mechanism for vasodilation of resistance arterioles to external agonists. Furthermore, pinacidil produces smooth muscle relaxation via both decreases in myosin light chain phosphorylation and actin depolymerization, whereas sodium nitroprusside produces smooth muscle relaxation primarily via actin depolymerization. NEW & NOTEWORTHY This article adds to the accumulating evidence on the contribution of the actin cytoskeleton to the regulation of vascular smooth muscle tone in resistance arterioles. Actin depolymerization appears to be an important mechanism for vasodilation of resistance arterioles to pharmacological agonists. Dilation to the K+ channel opener pinacidil is produced by decreases in myosin light chain phosphorylation and actin depolymerization, whereas dilation to the nitric oxide donor sodium nitroprusside occurs primarily via actin depolymerization. Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/vascular-smooth-muscle-actin-depolymerization/ .
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Carlson, Brian E., Julia C. Arciero, and Timothy W. Secomb. "Theoretical model of blood flow autoregulation: roles of myogenic, shear-dependent, and metabolic responses." American Journal of Physiology-Heart and Circulatory Physiology 295, no. 4 (October 2008): H1572—H1579. http://dx.doi.org/10.1152/ajpheart.00262.2008.
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The autoregulation of blood flow, the maintenance of almost constant blood flow in the face of variations in arterial pressure, is characteristic of many tissue types. Here, contributions to the autoregulation of pressure-dependent, shear stress-dependent, and metabolic vasoactive responses are analyzed using a theoretical model. Seven segments, connected in series, represent classes of vessels: arteries, large arterioles, small arterioles, capillaries, small venules, large venules, and veins. The large and small arterioles respond actively to local changes in pressure and wall shear stress and to the downstream metabolic state communicated via conducted responses. All other segments are considered fixed resistances. The myogenic, shear-dependent, and metabolic responses of the arteriolar segments are represented by a theoretical model based on experimental data from isolated vessels. To assess autoregulation, the predicted flow at an arterial pressure of 130 mmHg is compared with that at 80 mmHg. If the degree of vascular smooth muscle activation is held constant at 0.5, there is a fivefold increase in blood flow. When myogenic variation of tone is included, flow increases by a factor of 1.66 over the same pressure range, indicating weak autoregulation. The inclusion of both myogenic and shear-dependent responses results in an increase in flow by a factor of 2.43. A further addition of the metabolic response produces strong autoregulation with flow increasing by a factor of 1.18 and gives results consistent with experimental observation. The model results indicate that the combined effects of myogenic and metabolic regulation overcome the vasodilatory effect of the shear response and lead to the autoregulation of blood flow.
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Jackson, William F., and Erika M. Boerman. "Voltage-gated Ca2+channel activity modulates smooth muscle cell calcium waves in hamster cremaster arterioles." American Journal of Physiology-Heart and Circulatory Physiology 315, no. 4 (October 1, 2018): H871—H878. http://dx.doi.org/10.1152/ajpheart.00292.2018.
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Cremaster muscle arteriolar smooth muscle cells (SMCs) display inositol 1,4,5-trisphosphate receptor-dependent Ca2+waves that contribute to global myoplasmic Ca2+concentration and myogenic tone. However, the contribution made by voltage-gated Ca2+channels (VGCCs) to arteriolar SMC Ca2+waves is unknown. We tested the hypothesis that VGCC activity modulates SMC Ca2+waves in pressurized (80 cmH2O/59 mmHg, 34°C) hamster cremaster muscle arterioles loaded with Fluo-4 and imaged by confocal microscopy. Removal of extracellular Ca2+dilated arterioles (32 ± 3 to 45 ± 3 μm, n = 15, P < 0.05) and inhibited the occurrence, amplitude, and frequency of Ca2+waves ( n = 15, P < 0.05), indicating dependence of Ca2+waves on Ca2+influx. Blockade of VGCCs with nifedipine (1 μM) or diltiazem (10 μM) or deactivation of VGCCs by hyperpolarization of smooth muscle with the K+channel agonist cromakalim (10 μM) produced similar inhibition of Ca2+waves ( P < 0.05). Conversely, depolarization of SMCs with the K+channel blocker tetraethylammonium (1 mM) constricted arterioles from 26 ± 3 to 14 ± 2 μm ( n = 11, P < 0.05) and increased wave occurrence (9 ± 3 to 16 ± 3 waves/SMC), amplitude (1.6 ± 0.07 to 1.9 ± 0.1), and frequency (0.5 ± 0.1 to 0.9 ± 0.2 Hz, n = 10, P < 0.05), effects that were blocked by nifedipine (1 μM, P < 0.05). Similarly, the VGCC agonist Bay K8644 (5 nM) constricted arterioles from 14 ± 1 to 8 ± 1 μm and increased wave occurrence (3 ± 1 to 10 ± 1 waves/SMC) and frequency (0.2 ± 0.1 to 0.6 ± 0.1 Hz, n = 6, P < 0.05), effects that were unaltered by ryanodine (50 μM, n = 6, P > 0.05). These data support the hypothesis that Ca2+waves in arteriolar SMCs depend, in part, on the activity of VGCCs.NEW & NOTEWORTHY Arterioles that control blood flow to and within skeletal muscle depend on Ca2+influx through voltage-gated Ca2+channels and release of Ca2+from internal stores through inositol 1,4,5-trisphosphate receptors in the form of Ca2+waves to maintain pressure-induced smooth muscle tone.
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Kozma, Fruzsina, Robert A. Johnson, Fan Zhang, Changhua Yu, Xianglan Tong, and Alberto Nasjletti. "Contribution of endogenous carbon monoxide to regulation of diameter in resistance vessels." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 276, no. 4 (April 1, 1999): R1087—R1094. http://dx.doi.org/10.1152/ajpregu.1999.276.4.r1087.
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Endogenous carbon monoxide was proposed to subserve vasodepressor functions. If so, inhibition of heme oxygenase may be expected to promote vascular contraction. This hypothesis was examined in large and small arteries and in isolated first-order gracilis muscle arterioles of rat. The heme oxygenase inhibitors chromium mesoporphyrin (CrMP) and cobalt protoporphyrin (0.175–102 μmol/l) decreased the diameter of pressurized (80 mmHg) gracilis muscle arterioles, whereas magnesium protoporphyrin, a weak heme oxygenase inhibitor, did not. CrMP also elicited development of isometric tension in the muscular branch of the femoral artery but not in the aorta or femoral artery. Arteriolar constrictor responses to CrMP varied in relation to the intravascular pressure, were blunted in preparations exposed to exogenous carbon monoxide (100 μmol/l), and were unaffected by an endothelin receptor antagonist. Importantly, CrMP amplified the constrictor response to increases of pressure in gracilis arterioles. Accordingly, the constrictor effect of heme oxygenase inhibitors is attributable to magnification of myogenic tone due to withdrawal of a vasodilatory mechanism mediated by endogenous carbon monoxide. The study suggests that the vascular carbon monoxide system plays a role in the regulation of basal tone in resistance vessels.
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Cornelissen, Annemiek J. M., Jenny Dankelman, Ed VanBavel, and Jos A. E. Spaan. "Balance between myogenic, flow-dependent, and metabolic flow control in coronary arterial tree: a model study." American Journal of Physiology-Heart and Circulatory Physiology 282, no. 6 (June 1, 2002): H2224—H2237. http://dx.doi.org/10.1152/ajpheart.00491.2001.
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Myogenic response, flow-dependent dilation, and direct metabolic control are important mechanisms controlling coronary flow. A model was developed to study how these control mechanisms interact at different locations in the arteriolar tree and to evaluate their contribution to autoregulatory and metabolic flow control. The model consists of 10 resistance compartments in series, each representing parallel vessel units, with their diameters determined by tone depending on either flow and pressure [flow-dependent tone reduction factor (TRFflow) × Tonemyo] or directly on metabolic factors (Tonemeta). The pressure-Tonemyo and flow-TRFflow relations depend on the vessel size obtained from interpolation of data on isolated vessels. Flow-dependent dilation diminishes autoregulatory properties compared with pressure-flow lines obtained from vessels solely influenced by Tonemyo. By applying Tonemeta to the four distal compartments, the autoregulatory properties are restored and tone is equally distributed over the compartments. Also, metabolic control and blockage of nitric oxide are simulated. We conclude that a balance is required between the flow-dependent properties upstream and the constrictive metabolic properties downstream. Myogenic response contributes significantly to flow regulation.
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Ungvari, Zoltan, Pal Pacher, and Akos Koller. "Serotonin Reuptake Inhibitor Fluoxetine Decreases Arteriolar Myogenic Tone by Reducing Smooth Muscle [Ca2+]i." Journal of Cardiovascular Pharmacology 35, no. 6 (June 2000): 849–54. http://dx.doi.org/10.1097/00005344-200006000-00004.
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Sun, D., G. Kaley, and A. Koller. "Characteristics and origin of myogenic response in isolated gracilis muscle arterioles." American Journal of Physiology-Heart and Circulatory Physiology 266, no. 3 (March 1, 1994): H1177—H1183. http://dx.doi.org/10.1152/ajpheart.1994.266.3.h1177.
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Responses to changes in intravascular pressure of isolated rat gracilis muscle arterioles were investigated under no-flow conditions. First-, second-, and third- order arterioles were isolated and cannulated. Vascular diameters were measured with an image-shearing device and then recorded. In response to the step increases in perfusion pressure (from 20 to 160 mmHg, by 10- or 20-mmHg steps) arterioles constricted and developed active tone. For example, at 100, 80, and 50 mmHg pressure the steady-state active diameters of 1st-, 2nd-, and 3rd-order arterioles were 76.9 +/- 1.6, 32.3 +/- 1.1 and 22.3 +/- 3.2 microns, respectively. At the same perfusion pressure, by use of a Ca(2+)-free solution (ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid; 1 mM) containing sodium nitroprusside (SNP; 10(-4) M), the passive diameters (PD) of these vessels were 161.8 +/- 3.2, 76.0 +/- 1.7, and 47.6 +/- 2.2 microns. The negative slopes of the pressure-diameter curves indicate that in the physiological pressure range an inverse relationship exists between the arteriolar diameter and intravascular pressure. The maximum constriction expressed as a percent of PD was similar in the various sized arterioles (approximately 60%) but was reached at lower pressures in the smaller vessels. The vasoactive function of endothelium and vascular smooth muscle was assessed by the responses of arterioles to acetylcholine (ACh; 10(-6) M) and SNP (5 x 10(-8) M) before and after removal of the endothelium with air. After removal of the endothelium, dilation to ACh was abolished while dilation to SNP was retained.(ABSTRACT TRUNCATED AT 250 WORDS)
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D'Angelo, G., J. E. Mogford, G. E. Davis, M. J. Davis, and G. A. Meininger. "Integrin-mediated reduction in vascular smooth muscle [Ca2+]i induced by RGD-containing peptide." American Journal of Physiology-Heart and Circulatory Physiology 272, no. 4 (April 1, 1997): H2065—H2070. http://dx.doi.org/10.1152/ajpheart.1997.272.4.h2065.
Full textAbstract:
It has previously been shown that synthetic peptides containing the sequence arginine-glycine-aspartic acid (RGD) cause vasodilation by activation of alpha(v)beta3-integrin present on vascular smooth muscle (VSM) cells. The purpose of this study was to determine whether this dilatory effect is mediated by a reduction in VSM cytosolic Ca2+ concentration ([Ca2+]i). First-order arterioles from the rat cremaster were isolated, cannulated, and pressurized. [Ca2+]i was quantitated from the ratio of emitted fluorescence intensity during alternate excitation of fura 2-loaded vessels at 340 and 380 nm. Cyclo(-Arg-Gly-Asp-D-Phe-Val) (cycloRGD; 0.21-210 microM) produced a concentration-dependent dilation of arterioles that had developed basal myogenic tone. Over the entire concentration range tested, [Ca2+]i decreased from 91 +/- 6 to 27 +/- 4 nM (69.7 +/- 5.0% reduction). In association with the decrease in [Ca2+]i, arteriolar lumen diameter increased from 89 +/- 8 to 184 +/- 8 pm (89.8 +/- 1.8% dilation). At intermediate concentrations, cycloRGD induced rhythmic spiking of Ca2+ superimposed on the concentration-dependent lowering of basal [Ca2+]i. These data directly link integrin activation with alterations in Ca2+ regulation, the net effect of which is a reduction in [Ca2+]i. These data further suggest that integrins, through their role in mediating cellular attachment to the extracellular matrix and in cellular signaling involving Ca2+, could provide a logical link to mechanotransduction and myogenic phenomena.
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Kurjiaka, D. T., and S. S. Segal. "Autoregulation during pressor response elevates wall shear rate in arterioles." Journal of Applied Physiology 80, no. 2 (February 1, 1996): 598–604. http://dx.doi.org/10.1152/jappl.1996.80.2.598.
Full textAbstract:
Autoregulation of blood flow implies reciprocal changes in vessel diameter and red blood cell velocity (VRBC) when perfusion pressure is altered. We tested two hypotheses: 1) blood flow will be autoregulated throughout arteriolar networks during a pressor response, and 2) wall shear rate (WSR; proportional to VRBC/diameter) will increase during autoregulation. Male hamsters (109 +/- 3 g; n = 22) were anesthetized (pentobarbital sodium 60 mg/kg), and the cremaster muscle was prepared for intravital videomicroscopy. Internal diameter and VRBC were monitored in first (1A)- through fourth (4A)-order arterioles; WSR and blood flow were calculated. Data were acquired at rest and at the peak of diameter responses to bilateral carotid artery occlusion (CAO). At rest, 1) mean arterial and 1A transmural pressures were 100 +/- 5 and 59 +/- 4 mmHg, respectively; 2) as branch order increased, arteriolar diameter, VRBC, and blood flow decreased (P < 0.05); and 3) WSR and resting tone increased with branch order (P < 0.05). During pressor responses to CAO, 1) arterial and 1A pressures increased to 145 +/- 7 and 89 +/- 5 mmHg, respectively (P < 0.05); 2) 1A branches dilated while 2A, 3A, and 4A branches constricted (P < 0.05); 3) VRBC and WSR increased in all branches (P<0.05); and 4) blood flow increased in 1A and 2A branches (P < 0.05), yet was unchanged (i.e., was autoregulated) in 3A and 4A branches. Arteriolar constrictions during CAO were not affected by alpha-adrenoceptor blockade with phentolamine (10(-6) M). We conclude that autoregulation of muscle blood flow during a pressor response involves myogenic constriction of arterioles with concomitant elevation of WSR.
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Roy, Tuhin K., Axel R. Pries, and Timothy W. Secomb. "Theoretical comparison of wall-derived and erythrocyte-derived mechanisms for metabolic flow regulation in heterogeneous microvascular networks." American Journal of Physiology-Heart and Circulatory Physiology 302, no. 10 (May 15, 2012): H1945—H1952. http://dx.doi.org/10.1152/ajpheart.01176.2011.
Full textAbstract:
The objective of this study is to compare the effectiveness of metabolic signals derived from erythrocytes and derived from the vessel wall for regulating blood flow in heterogeneous microvascular networks. A theoretical model is used to simulate blood flow, mass transport, and vascular responses. The model accounts for myogenic, shear-dependent, and metabolic flow regulation. Metabolic signals are assumed to be propagated upstream along vessel walls via a conducted response. Arteriolar tone is assumed to depend on the conducted metabolic signal as well as local wall shear stress and wall tension, and arteriolar diameters are calculated based on vascular smooth muscle mechanics. The model shows that under certain conditions metabolic regulation based on wall-derived signals can be more effective in matching perfusion to local oxygen demand relative to regulation based on erythrocyte-derived signals, resulting in higher extraction and lower oxygen deficit. The lower effectiveness of the erythrocyte-derived signal is shown to result in part from the unequal partition of hematocrit at diverging bifurcations, such that low-flow vessels tend to receive a reduced hematocrit and thereby experience a reduced erythrocyte-derived metabolic signal. The model simulations predict that metabolic signals independent of erythrocytes may play an important role in local metabolic regulation of vascular tone and flow distribution in heterogeneous microvessel networks.
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Csekő, Csongor, Zsolt Bagi, and Akos Koller. "Biphasic effect of hydrogen peroxide on skeletal muscle arteriolar tone via activation of endothelial and smooth muscle signaling pathways." Journal of Applied Physiology 97, no. 3 (September 2004): 1130–37. http://dx.doi.org/10.1152/japplphysiol.00106.2004.
Full textAbstract:
We hypothesized that hydrogen peroxide (H2O2) has a role in the local regulation of skeletal muscle blood flow, thus significantly affecting the myogenic tone of arterioles. In our study, we investigated the effects of exogenous H2O2 on the diameter of isolated, pressurized (at 80 mmHg) rat gracilis skeletal muscle arterioles (diameter of ∼150 μm). Lower concentrations of H2O2 (10−6–3 × 10−5 M) elicited constrictions, whereas higher concentrations of H2O2 (6 × 10−5–3 × 10−4 M), after initial constrictions, caused dilations of arterioles (at 10−4 M H2O2, −19 ± 1% constriction and 66 ± 4% dilation). Endothelium removal reduced both constrictions (to −10 ± 1%) and dilations (to 33 ± 3%) due to H2O2. Constrictions due to H2O2 were completely abolished by indomethacin and the prostaglandin H2/thromboxane A2 (PGH2/TxA2) receptor antagonist SQ-29548. Dilations due to H2O2 were significantly reduced by inhibition of nitric oxide synthase (to 38 ± 7%) but were unaffected by clotrimazole or sulfaphenazole (inhibitors of cytochrome P-450 enzymes), indomethacin, or SQ-29548. In endothelium-denuded arterioles, clotrimazole had no effect, whereas H2O2-induced dilations were significantly reduced by charybdotoxin plus apamin, inhibitors of Ca2+-activated K+ channels (to 24 ± 3%), the selective blocker of ATP-sensitive K+ channels glybenclamide (to 14 ± 2%), and the nonselective K+-channel inhibitor tetrabutylammonium (to −1 ± 1%). Thus exogenous administration of H2O2 elicits 1) release of PGH2/TxA2 from both endothelium and smooth muscle, 2) release of nitric oxide from the endothelium, and 3) activation of K+ channels, such as Ca2+-activated and ATP-sensitive K+ channels in the smooth muscle resulting in biphasic changes of arteriolar diameter. Because H2O2 at low micromolar concentrations activates several intrinsic mechanisms, we suggest that H2O2 contributes to the local regulation of skeletal muscle blood flow in various physiological and pathophysiological conditions.
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Carlström, Mattias, Christopher S. Wilcox, and William J. Arendshorst. "Renal Autoregulation in Health and Disease." Physiological Reviews 95, no. 2 (April 2015): 405–511. http://dx.doi.org/10.1152/physrev.00042.2012.
Full textAbstract:
Intrarenal autoregulatory mechanisms maintain renal blood flow (RBF) and glomerular filtration rate (GFR) independent of renal perfusion pressure (RPP) over a defined range (80–180 mmHg). Such autoregulation is mediated largely by the myogenic and the macula densa-tubuloglomerular feedback (MD-TGF) responses that regulate preglomerular vasomotor tone primarily of the afferent arteriole. Differences in response times allow separation of these mechanisms in the time and frequency domains. Mechanotransduction initiating the myogenic response requires a sensing mechanism activated by stretch of vascular smooth muscle cells (VSMCs) and coupled to intracellular signaling pathways eliciting plasma membrane depolarization and a rise in cytosolic free calcium concentration ([Ca2+]i). Proposed mechanosensors include epithelial sodium channels (ENaC), integrins, and/or transient receptor potential (TRP) channels. Increased [Ca2+]ioccurs predominantly by Ca2+influx through L-type voltage-operated Ca2+channels (VOCC). Increased [Ca2+]iactivates inositol trisphosphate receptors (IP3R) and ryanodine receptors (RyR) to mobilize Ca2+from sarcoplasmic reticular stores. Myogenic vasoconstriction is sustained by increased Ca2+sensitivity, mediated by protein kinase C and Rho/Rho-kinase that favors a positive balance between myosin light-chain kinase and phosphatase. Increased RPP activates MD-TGF by transducing a signal of epithelial MD salt reabsorption to adjust afferent arteriolar vasoconstriction. A combination of vascular and tubular mechanisms, novel to the kidney, provides for high autoregulatory efficiency that maintains RBF and GFR, stabilizes sodium excretion, and buffers transmission of RPP to sensitive glomerular capillaries, thereby protecting against hypertensive barotrauma. A unique aspect of the myogenic response in the renal vasculature is modulation of its strength and speed by the MD-TGF and by a connecting tubule glomerular feedback (CT-GF) mechanism. Reactive oxygen species and nitric oxide are modulators of myogenic and MD-TGF mechanisms. Attenuated renal autoregulation contributes to renal damage in many, but not all, models of renal, diabetic, and hypertensive diseases. This review provides a summary of our current knowledge regarding underlying mechanisms enabling renal autoregulation in health and disease and methods used for its study.
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Sun, D., A. Huang, A. Koller, and G. Kaley. "Short-term daily exercise activity enhances endothelial NO synthesis in skeletal muscle arterioles of rats." Journal of Applied Physiology 76, no. 5 (May 1, 1994): 2241–47. http://dx.doi.org/10.1152/jappl.1994.76.5.2241.
Full textAbstract:
We aimed to test the hypothesis that as a consequence of short-term daily bouts of exercise the control of arteriolar smooth muscle by endothelium is altered. Rats ran on a treadmill once a day, 5 days/wk, for 2–4 wk (with gradually increasing intensity, up to 26 min at 22 m/min at a 1% grade by the beginning of the 3rd wk and up to 38 min at 28 m/min at a 2% grade by the beginning of the 4th wk) while a control group remained sedentary (SED). Cannulated and pressurized arterioles of rat gracilis muscle developed spontaneous myogenic tone, which was slightly enhanced in exercised (EX) compared with SED rat arterioles. At 80 mmHg pressure, the passive (Ca(2+)-free solution) and active diameters of SED and EX rat arterioles were 105.4 +/- 3.8 and 55.1 +/- 2.3 microns and 107.1 +/- 3.4 and 50.2 +/- 2.2 microns, respectively. Dose-dependent dilations to sodium nitroprusside (10(-8)-10(-6) M) and constrictions to norepinephrine (10(-8)-10(-6) M) were not affected in EX arterioles, whereas dilations to adenosine (10(-6)-10(-4) M) were significantly reduced. In contrast, dose-dependent dilations to acetylcholine (ACh; 5 x 10(-9)-10(-7) M) and L-arginine [precursor of nitric oxide (NO); 10(-4)-10(-3) M] were significantly enhanced (by 33–78 and 57–75%, respectively) in arterioles of EX compared with those of SED rats. Responses of arterioles to sodium nitrite were not different in SED and EX groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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Barkoudah, Ebrahim, Jonathan H. Jaggar, and Charles W. Leffler. "The permissive role of endothelial NO in CO-induced cerebrovascular dilation." American Journal of Physiology-Heart and Circulatory Physiology 287, no. 4 (October 2004): H1459—H1465. http://dx.doi.org/10.1152/ajpheart.00369.2004.
Full textAbstract:
Carbon monoxide (CO) and nitric oxide (NO) are important paracrine messengers in the newborn cerebrovasculature that may act as comessengers. Here, we investigated the role of NO in CO-mediated dilations in the newborn cerebrovasculature. Arteriolar branches of the middle cerebral artery (100–200 μm) were isolated from 3- to 7-day-old piglets and cannulated at each end in a superfusion chamber, and intravascular pressure was elevated to 30 mmHg, which resulted in the development of myogenic tone. Endothelium removal abolished dilations of pressurized pial arterioles to bradykinin and to the CO-releasing molecule Mn2(CO)10 [dimanganese decacarbonyl (DMDC)] but not dilations to isoproterenol. With endothelium intact, Nω-nitro-l-arginine (l-NNA), 1 H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ), or tetraethylammonium chloride (TEA+), inhibitors of NO synthase (NOS), guanylyl cyclase, and large-conductance Ca2+-activated K+ (KCa) channels, respectively, also blocked dilation induced by DMDC. After inhibition of NOS, a constant concentration of sodium nitroprusside (SNP), a NO donor that only dilated the vessel 6%, returned dilation to DMDC. The stable cGMP analog 8-bromo-cGMP also restored dilation to DMDC in endothelium-intact, l-NNA-treated, or endothelium-denuded arterioles, and this effect was blocked by TEA+. Similarly, in the continued presence of ODQ, 8-bromo-cGMP restored DMDC-induced dilations. These findings suggest that endothelium-derived NO stimulates guanylyl cyclase in vascular smooth muscle cells and, thereby, permits CO to cause dilation by activating KCa channels. Such a requirement for NO could explain the endothelium dependency of CO-induced dilation in piglet pial arterioles.
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Altura, B. M., B. T. Altura, A. Carella, A. Gebrewold, T. Murakawa, and A. Nishio. "Mg2+–Ca2+ interaction in contractility of vascular smooth muscle: Mg2+ versus organic calcium channel blockers on myogenic tone and agonist-induced responsiveness of blood vessels." Canadian Journal of Physiology and Pharmacology 65, no. 4 (April 1, 1987): 729–45. http://dx.doi.org/10.1139/y87-120.
Full textAbstract:
Contractility of all types of invertebrate and vertebrate muscle is dependent upon the actions and interactions of two divalent cations, viz., calcium (Ca2+) and magnesium (Mg2+) ions. The data presented and reviewed herein contrast the actions of several organic Ca2+ channel blockers with the natural, physiologic (inorganic) Ca2+ antagonist, Mg2+, on microvascular and macrovascular smooth muscles. Both direct in vivo studies on microscopic arteriolar and venular smooth muscles and in vitro studies on different types of blood vessels are presented. It is clear from the studies done so far that of all Ca2+ antagonists examined, only Mg2+ has the capability to inhibit myogenic, basal, and hormonal-induced vascular tone in all types of vascular smooth muscle. Data obtained with verapamil, nimopidine, nitrendipine, and nisoldipine on the microvasculature are suggestive of the probability that a heterogeneity of Ca2+ channels, and of Ca2+ binding sites, exists in different microvascular smooth muscles; although some appear to be voltage operated and others, receptor operated, they are probably heterogeneous in composition from one vascular region to another. Mg2+ appears to act on voltage-, receptor-, and leak-operated membrane channels in vascular smooth muscle. The organic Ca2+ channel blockers do not have this uniform capability; they demonstrate a selectivity when compared with Mg2+. Mg2+ appears to be a special kind of Ca2+ channel antagonist in vascular smooth muscle. At vascular membranes it can (i) block Ca2+ entry and exit, (ii) lower peripheral and cerebral vascular resistance, (iii) relieve cerebral, coronary, and peripheral vasospasm, and (iv) lower arterial blood pressure. At micromolar concentrations (i.e., 10–100 μM), Mg2+ can cause significant vasodilatation of intact arterioles and venules in all regional vasculatures so far examined. Although Mg2+ is three to five orders of magnitude less potent than the organic Ca2+ channel blockers, it possesses unique and potentially useful Ca2+ antagonistic properties.
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COATS, P. "Myogenic, mechanical and structural characteristics of resistance arterioles from healthy and ischaemic subjects." Clinical Science 105, no. 6 (December 1, 2003): 683–89. http://dx.doi.org/10.1042/cs20030203.
Full textAbstract:
In critical limb ischaemia (CLI), the ability to regulate regional blood flow in the diseased portion of the leg would appear to be severely compromised. Considering this, pressure-dependent myogenic and mechanical properties of resistance arterioles isolated from control subjects and from patients with CLI were studied. Using confocal microscopy and pressure myography, subcutaneous resistance arteriole structure and function were compared between subcutaneous arterioles isolated from healthy volunteers [control subcutaneous (CS)] and non-diseased proximal subcutaneous (PS; internal control) and distal subcutaneous (DS) arterioles from the diseased ischaemic part of the limb from patients with CLI. Significant wall atrophy was observed in DS arterioles compared with PS and CS arterioles. Passive pressure-dependent mechanical properties were significantly altered in the diseased arterioles compared with PS and CS arterioles. Active pressure-dependent myogenic tone was completely absent in DS arterioles. The atrophic structural remodelling in DS arterioles were correlated with the changes in vascular mechanics, but not with the ability of these arterioles to contract in response to chemical stimuli. However, active pressure-dependent myogenic tone was absent in the DS arterioles. The combination of altered pressure-dependent passive mechanical and active myogenic tone goes some way in explaining CLI sequelae and poor outcome following surgical revascularization experienced by these patients.
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Laughlin, M. Harold, Douglas K. Bowles, and Dirk J. Duncker. "The coronary circulation in exercise training." American Journal of Physiology-Heart and Circulatory Physiology 302, no. 1 (January 2012): H10—H23. http://dx.doi.org/10.1152/ajpheart.00574.2011.
Full textAbstract:
Exercise training (EX) induces increases in coronary transport capacity through adaptations in the coronary microcirculation including increased arteriolar diameters and/or densities and changes in the vasomotor reactivity of coronary resistance arteries. In large animals, EX increases capillary exchange capacity through angiogenesis of new capillaries at a rate matched to EX-induced cardiac hypertrophy so that capillary density remains normal. However, after EX coronary capillary exchange area is greater (i.e., capillary permeability surface area product is greater) at any given blood flow because of altered coronary vascular resistance and matching of exchange surface area and blood flow distribution. The improved coronary capillary blood flow distribution appears to be the result of structural changes in the coronary tree and alterations in vasoreactivity of coronary resistance arteries. EX also alters vasomotor reactivity of conduit coronary arteries in that after EX, α-adrenergic receptor responsiveness is blunted. Of interest, α- and β-adrenergic tone appears to be maintained in the coronary microcirculation in the presence of lower circulating catecholamine levels because of increased receptor responsiveness to adrenergic stimulation. EX also alters other vasomotor control processes of coronary resistance vessels. For example, coronary arterioles exhibit increased myogenic tone after EX, likely because of a calcium-dependent PKC signaling-mediated alteration in voltage-gated calcium channel activity in response to stretch. Conversely, EX augments endothelium-dependent vasodilation throughout the coronary arteriolar network and in the conduit arteries in coronary artery disease (CAD). The enhanced endothelium-dependent dilation appears to result from increased nitric oxide bioavailability because of changes in nitric oxide synthase expression/activity and decreased oxidant stress. EX also decreases extravascular compressive forces in the myocardium at rest and at comparable levels of exercise, mainly because of decreases in heart rate and duration of systole. EX does not stimulate growth of coronary collateral vessels in the normal heart. However, if exercise produces ischemia, which would be absent or minimal under resting conditions, there is evidence that collateral growth can be enhanced. While there is evidence that EX can decrease the progression of atherosclerotic lesions or even induce the regression of atherosclerotic lesions in humans, the evidence of this is not strong due to the fact that most prospective trials conducted to date have included other lifestyle changes and treatment strategies by necessity. The literature from large animal models of CAD also presents a cloudy picture concerning whether EX can induce the regression of or slow the progression of atherosclerotic lesions. Thus, while evidence from research using humans with CAD and animal models of CAD indicates that EX increases endothelium-dependent dilation throughout the coronary vascular tree, evidence that EX reverses or slows the progression of lesion development in CAD is not conclusive at this time. This suggests that the beneficial effects of EX in CAD may not be the result of direct effects on the coronary artery wall. If this suggestion is true, it is important to determine the mechanisms involved in these beneficial effects.
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Janssen, Ben J. A., Elena V. Lukoshkova, and Geoffrey A. Head. "Sympathetic modulation of renal blood flow by rilmenidine and captopril: central vs. peripheral effects." American Journal of Physiology-Renal Physiology 282, no. 1 (January 1, 2002): F113—F123. http://dx.doi.org/10.1152/ajprenal.0153.2001.
Full textAbstract:
Renal blood flow (RBF) is modulated by renal sympathetic nerve activity (RSNA). However, agents that are supposed to reduce sympathetic tone, such as rilmenidine and captopril, influence RBF also by direct arteriolar effects. The present study was designed to test to what extent the renal nerves contribute to the renal hemodynamic response to rilmenidine and captopril. We used a technique that allows simultaneous recording of RBF and RSNA to the same kidney in conscious rabbits. We compared the dose-dependent effects of rilmenidine (0.01–1 mg/kg) and captopril (0.03–3 mg/kg) on RBF and RSNA in intact and renal denervated (RNX) rabbits. Because rilmenidine and captopril lower blood pressure, studies were also performed in sinoaortically denervated (SAD) rabbits to determine the role of the baroreflex in the renal hemodynamic response. Rilmenidine reduced arterial pressure, RBF, and RSNA dose dependently. In intact rabbits ( n = 10), renal conductance (RC) remained unaltered (3 ± 5%), even after the 1-mg/kg dose, which completely abolished RSNA. In RNX rabbits ( n = 6), RC fell by 18 ± 5%, whereas in SAD rabbits ( n = 7) RC increased by 30 ± 20% after rilmenidine. In intact rabbits, captopril increased RSNA maximally by 64 ± 8%. RSNA did not rise in SAD rabbits. Despite the differential response or absence of RSNA, captopril increased RC to a comparable degree (maximally 40–50%) in all three groups. Using spectral analysis techniques, we found that in all groups, independently of ongoing RSNA, captopril, but not rilmenidine, attenuated both myogenic (0.07–0.25 Hz) and tubuloglomerular feedback (0.01–0.07 Hz) related fluctuations in RC. We conclude that, in conscious rabbits, the renal vasodilator effect of rilmenidine depends on the level of ongoing RSNA. Its sympatholytic effect is, however, blunted by a direct arteriolar vasoconstrictor effect. In contrast, the renal vasodilator effect of captopril is not modulated by ongoing RSNA and is associated with impairment of autoregulation of RBF.
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Ge, Ying, Kimberly Gannon, Monette Gousset, Ruishing Liu, Beau Murphey, and Heather A. Drummond. "Impaired myogenic constriction of the renal afferent arteriole in a mouse model of reduced βENaC expression." American Journal of Physiology-Renal Physiology 302, no. 11 (June 1, 2012): F1486—F1493. http://dx.doi.org/10.1152/ajprenal.00638.2011.
Full textAbstract:
Previous studies demonstrate a role for β epithelial Na+ channel (βENaC) protein as a mediator of myogenic constriction in renal interlobar arteries. However, the importance of βENaC as a mediator of myogenic constriction in renal afferent arterioles, the primary site of development of renal vascular resistance, has not been determined. We colocalized βENaC with smooth muscle α-actin in vascular smooth muscle cells in renal arterioles using immunofluorescence. To determine the importance of βENaC in myogenic constriction in renal afferent arterioles, we used a mouse model of reduced βENaC (βENaC m/m) and examined pressure-induced constrictor responses in the isolated afferent arteriole-attached glomerulus preparation. We found that, in response to a step increase in perfusion pressure from 60 to 120 mmHg, the myogenic tone increased from 4.5 ± 3.7 to 27.3 ± 5.2% in +/+ mice. In contrast, myogenic tone failed to increase with the pressure step in m/m mice (3.9 ± 0.8 to 6.9 ± 1.4%). To determine the importance of βENaC in myogenic renal blood flow (RBF) regulation, we examined the rate of change in renal vascular resistance following a step increase in perfusion pressure in volume-expanded animals. We found that, following a step increase in pressure, the rate of myogenic correction of RBF is inhibited by 75% in βENaC m/m mice. These findings demonstrate that myogenic constriction in afferent arterioles is dependent on normal expression of βENaC.
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Yamasaki, Evan, Pratish Thakore, Vivek Krishnan, and Scott Earley. "Differential expression of angiotensin II type 1 receptor subtypes within the cerebral microvasculature." American Journal of Physiology-Heart and Circulatory Physiology 318, no. 2 (February 1, 2020): H461—H469. http://dx.doi.org/10.1152/ajpheart.00582.2019.
Full textAbstract:
Arteries and arterioles constrict in response to intraluminal pressure to generate myogenic tone, but the molecular nature of the vascular force-sensing mechanism is not fully characterized. Here, we investigated the role of angiotensin II type 1 receptors (AT1Rs) on vascular smooth muscle cells in the development of myogenic tone in cerebral parenchymal arterioles from mice. We found that pretreatment with the AT1R blocker losartan inhibited the development of myogenic tone in these vessels but did not alter the luminal diameter of arterioles with preestablished tone. Rodents express two AT1R isotypes: AT1Ra and AT1Rb. We previously demonstrated that AT1Rb is expressed at much higher levels compared with AT1Ra in cerebral pial arteries and is required for myogenic contractility in these vessels, whereas AT1Ra is unnecessary for this function. Here, we found that AT1Ra and AT1Rb are expressed at similar levels in parenchymal arterioles and that genetic knockout of AT1Ra blunted the ability of these vessels to generate myogenic tone. We also found that AT1Rb and total AT1R expression levels are much lower in parenchymal arterioles compared with pial arteries and that parenchymal arterioles are less sensitive to the vasoconstrictive effects of the endogenous AT1R ligand angiotensin II (ANG II). We conclude that 1) AT1Rs are critical for the initiation, but not the maintenance, of myogenic tone in parenchymal arterioles, and 2) lower levels of AT1Rb and total AT1R in parenchymal arterioles compared with pial arteries result in differences in myogenic and ANG II-induced vasoconstriction between these vascular segments. NEW & NOTEWORTHY Myogenic tone is critical for appropriate regulation of cerebral blood flow, but the mechanisms used by vascular smooth muscle cells to detect changes in intraluminal pressure are not fully characterized. Here, we demonstrate angiotensin II receptor type 1 (AT1R) is indispensable to initiation, but not maintenance, of myogenic tone in cerebral parenchymal arterioles. Furthermore, we demonstrate differences in AT1R expression levels lead to critical differences in contractile regulation between parenchymal arterioles and cerebral pial arteries.
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Kang, Lori S., SeJeong Kim, James M. Dominguez, Amy L. Sindler, Gregory M. Dick, and Judy M. Muller-Delp. "Aging and muscle fiber type alter K+ channel contributions to the myogenic response in skeletal muscle arterioles." Journal of Applied Physiology 107, no. 2 (August 2009): 389–98. http://dx.doi.org/10.1152/japplphysiol.91245.2008.
Full textAbstract:
Aging diminishes myogenic tone in arterioles from skeletal muscle. Recent evidence indicates that both large-conductance Ca2+-activated (BKCa) and voltage-dependent (KV) K+ channels mediate negative feedback control of the myogenic response. Thus we tested the hypothesis that aging increases the contributions of KV and BKCa channels to myogenic regulation of vascular tone. Because myogenic responsiveness differs between oxidative and glycolytic muscles, we predicted that KV and BKCa channel contributions to myogenic responsiveness vary with fiber type. Myogenic responses of first-order arterioles from the gastrocnemius and soleus muscles of 4- and 24-mo-old Fischer 344 rats were evaluated in the presence and absence of 4-aminopyridine (5 mM) or iberiotoxin (30 nM), inhibitors of KV and BKCa, respectively. 4-Aminopyridine enhanced myogenic tone with aging and normalized age-related differences in both muscle types. By contrast, iberiotoxin eliminated age-related differences in soleus arterioles and had no effect in gastrocnemius vessels. KV1.5 is an integral component of KV channels in vascular smooth muscle; therefore, we determined the relative protein expression of KV1.5, as well as BKCa, in soleus and gastrocnemius arterioles. Immunoblot analysis revealed no differences in KV1.5 protein with aging or between variant fiber types, whereas BKCa protein levels declined with age in arterioles from both muscle groups. Collectively, these results suggest that the contribution of BKCa to myogenic regulation of vascular tone changes with age in soleus muscle arterioles, whereas increased KV channel expression and negative feedback regulation of myogenic tone increases with advancing age in arterioles from both oxidative and glycolytic muscles.