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1
D'Oyley, Heather M. "Vasodilators and venous tone." Thesis, University of British Columbia, 1988. http://hdl.handle.net/2429/27871.
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The objective of these experiments was to investigate the effects of various membrane receptor-mediated and receptor-independent vasodilators on the resistance and capacitance vessels of conscious, unrestrained rats by measuring mean arterial pressure (MAP) and mean circulatory filling pressure (MCFP), an index of total body venous tone.
ln the first set of experiments the dose-response effects of the directly-acting vasodilators nitroglycerin, sodium nitroprusside and hydralazine were determined in intact rats as well as in rats treated with the ganglionic blocker, hexamethonium. The effects of these drugs were compared with those of the vehicle, normal saline, in control rats. In intact rats, iv infusion of nitroglycerin did not alter MAP while iv infusions of nitroprusside and hydralazine caused dose-dependent decreases in MAP. In intact rats, nitroglycerin and sodium nitroprusside did. not affect MCFP while hydralazine increased MCFP. After treatment with hexamethonium all three drugs decreased MCFP, though the decreases in MCFP caused by hydralazine were not significantly different from the corresponding changes in saline-treated rats. Therefore, sodium nitroprusside and hydralazine but not nitroglycerin were effective arteriolar dilators in intact rats; all three drugs dilated arterioles in ganglionic-blocked rats, ln intact rats, the direct venodilator actions of nitroprusside and nitroglycerin were masked by endogenous sympathetic tone. When sympathetic nerve activity was attenuated, both drugs had venodilatory effects. Hydralazine, on the other hand, hao insignificant venodilatory effects both in the presence and absence of the sympathetic reflexes. In the second set of experiments we determined the dose-response effects of hexamethonium, phentolamine, prazosin and rauwolscine — the latter being non-selective ⍺, ⍺₁-selective, and ⍺₂-selective adrenoceptor antagonists, respectively — in intact rats. Prazosin and rauwolscine were also administered to rats with reflexly increased venous tone induced by the infusion of hydralazine. In intact rats iv infusions of prazosin, phentolamine and rauwolscine all caused dose-dependent decreases in MAP; only rauwolscine reduced MCFP to levels slightly below control. Hexamethonium
caused a aecrease in MAP as well as a markea reduction in MCFP. After venous tone was raised by the infusion of hydralazine, both prazosin and rauwolscine dose-dependently decreased MCFP. Therefore, the resistance and capacitance vessels contain both ⍺₁- and ⍺₂-adrenoceptors. in the intact rat, however, the capacitance vessels are somewhat resistant to the effects of postjunctionally acting ⍺-antagonists in contrast to the effects of hexamethonium which acts at the level of the ganglion.Medicine, Faculty of
Anesthesiology, Pharmacology and Therapeutics, Department of
Graduate
2
Siddons, Thomas Edward. "The use of pulsed inhaled nitric oxide in the investigation and treatment of chronic disease affecting the pulmonary circulation." Thesis, University of Sheffield, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.274966.
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Talbot, Nicola Maria. "Metal nitrosyl and organic nitrates as novel vasodilators." Thesis, University of Exeter, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.385724.
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4
Weldon, Hazel. "The synthesis of novel nitric oxide donors as potential vasodilators." Thesis, University of Exeter, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.307295.
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5
Lo, Sze-man Irene. "A comparison of the vasoactive metabolites in the interstitial space of oxidative or glycolytic muscles in anaesthetised rats /." Hong Kong : University of Hong Kong, 2000. http://sunzi.lib.hku.hk/hkuto/record.jsp?B21790838.
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6
HYNES, MICHAEL RAY. "ENDOTHELIUM-DEPENDENT RELAXATION OF BLOOD VESSELS." Diss., The University of Arizona, 1987. http://hdl.handle.net/10150/184134.
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Dilation of blood vessels in response to a large number of agents has been shown to be dependent on an intact vascular endothelium. The present studies examine some aspects of endothelium-dependent vasodilation in blood vessels of the rabbit and rat. Using the rabbit ear artery and the subtype-selective muscarinic antagonist pirenzepine, muscarinic receptors of the endothelium and smooth muscle cells were shown to be of the low affinity M₂ subtype. Inhibition of [³H](-)quinuclidinyl benzilate was used to determine affinity for the smooth muscle receptors while antagonism of methacholine induced vasodilation yielded the endothelial cell receptor affinity. The effect of increasing age (1-27 months) on endothelium-dependent relaxation was studied in aortic rings, perfused tail artery and perfused mesenteric bed of the Fisher 344 rat. Both aortic ring segments and perfused caudal arteries showed an age-related increase in sensitivity of endothelium-mediated relaxation to the cholinergic agonist methacholine. This increased sensitivity occurs between the ages of 6 and 12 months, with no further significant increase up to 27 months of age, suggesting this is a consequence of growth and development rather than old age. No difference with age in cholinergic relaxation was observed in the perfused mesenteric bed indicating either no change of sensitivity in smaller resistance vessels or an effect which is hidden in this more complex perfused system. In contrast to findings with cholinergic stimution, responses of the perfused caudal artery to the calcium ionophore A23187 were not altered with age. This suggests that the alteration with age in response to methacholine involves the muscarinic receptor or receptor coupling mechanism rather than the generation of, or response to, endothelium-derived relaxing factor (EDRF). The influence of endothelium on contractile responses was examined using the perfused caudal artery. Endothelium removal significantly increased contraction to the α-adrenergic agonists methoxamine and BH-T 920 as well as to transmural nerve stimulation. Inhibition of contraction to agents which must first cross the smooth muscle layer before reaching the endothelium suggests that a continuous or basal level of EDRF release is responsible for decreased contraction rather than an receptor stimulated release of EDRF.
7
Reeves, Katherine Ann. "The cardiovascular actions of the isopropyl ester and other synthetic derivatives of palmitoyl carnitine." Thesis, University of Bath, 1995. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.260252.
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8
Joseph, Emlyn Clive. "Pathogenesis of arteriopathy induced by PDE III inhibitors in the rat and dog." Thesis, Queen Mary, University of London, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.307684.
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Firkin, Catherine R. "A biomimetic approach to the synthesis of xestospongin A." Thesis, University of Oxford, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.389208.
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10
羅詩敏 and Sze-man Irene Lo. "A comparison of the vasoactive metabolites in the interstitial space of oxidative or glycolytic muscles in anaesthetised rats." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2000. http://hub.hku.hk/bib/B31223138.
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11
Wier, S. W. "A study of the action of some vasodilators in the rat and guinea-pig." Thesis, University of Manchester, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.374572.
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McLeod, Janet Leigh, and janet mcleod@deakin edu au. "The natriuretic peptides and their receptors in the brain of the amphibian, Bufo marinus." Deakin University. School of Biological and Chemical Sciences, 1999. http://tux.lib.deakin.edu.au./adt-VDU/public/adt-VDU20071024.112730.
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The natriuretic peptides, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) are members of a family of hormones that play an important role in mammalian fluid and electrolyte balance. In the periphery, natriuretic peptides reduce blood volume and subsequently blood pressure by increasing renal natriuresis and diuresis and relaxation of vascular smooth muscle. The actions of natriuretic peptides are mediated via two membrane-linked guanylate cyclase receptors (NPR-GC); natriuretic peptide receptor-A (NPR-A) which has a high affinity for ANP and BNP; and natriuretic peptide receptor-B (NPR-B)which has the greatest affinity for CNP. A third receptor not linked to guanylate cyclase, natriuretic peptide receptor-C (NPR-C) also exists, which binds to ANP, BNP and CNP with a relatively equal affinity, and is involved with clearance of the peptides from the circulation and tissues. The natriuretic peptides are present in the brain and are particularly predominant in cardiovascular and fluid and electrolyte regulating areas such as the anteroventral third ventricle (AV3V) region. This distribution has led to the suggestion natriuretic peptides play a neuromodulatory role in the central control of fluid homeostasis. Natriuretic peptides in the brain have been observed to inhibit the release of other fluid and electrolyte regulating hormones such as arginine vasopressin (AVP) and angiotensin II (AII).
Natriuretic peptides have also been identified in the non-mammalian vertebrates although information regarding the distribution of the peptides and their receptors in the non-mammalian brain is limited. In amphibians, immunohistochemical studies have shown that natriuretic peptides are highly concentrated in the preoptic region of the brain, an area believed to be analogous to the A\T3\ region in mammals, which suggests that natriuretic peptides may also be involved in central fluid and electrolyte regulation in amphibians. To date, CNP is the only natriuretic peptide that has been isolated and cloned from the lower vertebrate brain, although studies on the distribution of CNP binding sites in the brain have only been performed in one fish species. Studies on the distribution of ANP binding sites in the lower vertebrate brain are similarly limited and have only been performed in one fish and two amphibian species. Moreover, the nature and distribution of the natriuretic peptide receptors has not been characterised. The current study therefore, used several approaches to investigate the distribution of natriuretic peptides and their receptors in the brain of the amphibian Bufo marinus. The topographical relationship of natriuretic peptides and the fluid and electrolyte regulating hormone arginine vasotocin was also investigated, in order to gain a greater understanding of the role of the natriuretic peptide system in the lower vertebrate brain.
Immunohistochemical studies showed natriuretic peptides were distributed throughout the brain and were highly concentrated in the preoptic region and interpeduncular nucleus. No natriuretic peptide-like immunoreactivity (NP-IR) was observed in the pituitary gland. Arginine vasotocin-like immunoreactivity (AvT-IR) was confined to distinct regions, particularly in the preoptic/hypothalamic region and pituitary gland. Double labelling studies of NP-JR and AvT-IR showed the peptides are not colocalised in the same neural pathways.
The distribution of natriuretic peptide binding sites using the ligands 125I-rat ANP (125I-rANP) and 125I-porcine CNP (125I-pCNP) showed different distributions in the brain of B. marinus. The specificity of binding was determined by displacement with unlabelled rat ANP, porcine CNP and C-ANF, an NPR-C specific ligand. 125I-rANP binding sites were broadly distributed throughout the brain with the highest concentration in pituitary gland, habenular, medial pallium and olfactory region. Minimal 125I-rANP binding was observed in the preoptic region. Residual 125I-rANP binding in the presence of C-ANF was observed in the olfactory region, habenular and pituitary gland indicating the presence of both NPR-GC and NPR-C in these regions. 125I-pCNP binding was limited to the olfactory region, pallium and posterior pituitary gland. All 125I-pCNP binding was displaced by C-ANF which suggests that CNP in the brain of B. marinus binds only to NPR-C.
Affinity cross-linking and SDS-PAGB demonstrated two binding sites at 136 kDa and 65 kDa under reducing conditions. Guanylate cyclase assays showed 0.1 µM ANP increased cGMP levels 50% above basal whilst a 10-fold higher concentration of CNP was required to produce the same result. Molecular cloning studies revealed a 669 base pair fragment showing 91% homology with human and rat NPR-A and 89% homology with human, rat and eel NPR-B. A 432 base pair fragment showing 67% homology to the mammalian NPR-C and 58% homology with eel NPR-D was also obtained.
The results show natriuretic peptides and their receptors are distributed throughout the brain of B. marinus which indicates that natriuretic peptides may participate in a range of regulatory functions throughout the brain. The potential for natriuretic peptides to regulate the release of the fluid and electrolyte regulating hormone AVT also exists due to the high number of natriuretic peptide binding sites in the posterior pituitary gland. At least two populations of natriuretic peptide receptors are present in the brain of B. marinus, one linked to guanylate cyclase and one resembling the mammalian clearance receptor. Furthermore, autoradiography and guanylate cyclase studies suggest ANP may be the major ligand in the brain of B. marinus, even though CNP is the only natriuretic peptide that has been isolated from the lower vertebrate brain to date.
13
Heeneman, Sylvia. "Structural alterations in peripheral arteries during experimental heart failure opposing effects of vasoconstrictors and vasodilators /." Maastricht : Maastricht : Universiteit Maastricht ; University Library, Maastricht University [Host], 1997. http://arno.unimaas.nl/show.cgi?fid=5813.
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14
Finch, Michael Brendan. "Haemodynamic effects of some peripheral vasodilators in normal man and in patients with Reynauds's syndrome." Thesis, Queen's University Belfast, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.328044.
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15
Schrage, William. "Effects of hindlimb unweighting on soleus muscle resistance artery endothelial function and eNOS expression." free to MU campus, to others for purchase, 2001. http://wwwlib.umi.com/cr/mo/fullcit?p3013020.
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16
Yin, Ning [Verfasser]. "Inhaled vasodilators as a new treatment strategy in pulmonary hypertension with left heart disease / Ning Yin." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2009. http://d-nb.info/1023580365/34.
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17
Tsoporis, Jim. "Effects of arterial vasodilators on cardiovascular hypertrophy and sympathetic activity in normotensive Wistar and spontaneously hypertensive rats." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp03/NQ66241.pdf.
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Gómez, Ortiz Edna Mireya [UNESP]. "Avaliação cardíaca de cães com degeneração valvar mixomatosa durante o emprego de enalapril, losartana, furosemida e suas combinações." Universidade Estadual Paulista (UNESP), 2011. http://hdl.handle.net/11449/89198.
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A degeneração valvar mixomatosa (DVM) é a afecção cardíaca mais comum em cães. O tratamento da insuficiência cardíaca congestiva (ICC) decorrente da DVM baseia-se no uso de inibidores da enzima conversora de angiotensina - ECA. Antagonistas dos receptores de angiotensina II - ARAs promovem o bloqueio completo da angiotensina II, e são usados no tratamento de ICC em humanos, mas não é comum em cães. O objetivo desta pesquisa foi comparar as respostas clínicas de cães com DVM tratados com enalapril- ECA, losartana -ARAs, furosemida – diurético de alça ou suas combinações. Vinte e nove cães foram distribuídos em cinco grupos dependendo da classe de ICC (Ib ou II) e do tratamento: G1 - Ib, enalapril; G2 – Ib, losartana; G3 – II, enalapril + furosemida; G4 – II, losartana + furosemida; G5- II, enalapril + losartana. Realizou-se exame físico, e determinaramse medidas eletrocardiográficas e pressão arterial nos dias 0, 14, 28 e 56 após início dos tratamentos. Medida radiográfica - Vertebral Heart Size, e variáveis ecodopplercardiográficas obtiveram-se nos dias 0 e 56. Submeteram-se os dados a analise de variância com medidas repetidas. Não houve diferenças (P>0,05) nas variáveis ecodopplercardiográficas, eletrocardiográficas e radiográficas quando comparados cães tratados com enalapril, losartana e suas combinações, tanto com ICC da classe Ib quanto da II. Nos cães de todos os grupos houve diminuição (P> 0,05), a través do tempo, da Vertebral Heart Size e redução (P> 0,05) da duração da onda P e do complexo QRS. Concluiu-se que losartana atua de forma similar ao enalapril no tratamento inicial (primeiros 56 dias) de cães com DVM em fases Ib e II da ICC
Degenerative myxomatous mitral valve disease (DMMVD) is the most common cardiac disease in dogs. The treatment of congestive heart failure (CHF) due to DMMVD is based, among others, on the use of vasodilators, like angiotensin converting enzyme (ACE) inhibitors. Recently, other vasodilators such as angiotensin II receptor antagonists (ARAs) have been used in humans with CHF and have promoted a complete blockage of angiotensin II, but is not common in dogs. Thus, the purpose of this investigation was to compare clinical outcomes of enalapril- ACA , losartan - ARAs, furosemide loop diuretic and its combinations in the treatment of CHF in dogs with DMMVD. For this, 29 dogs were distributed into five groups regardless of class of CHF (Ib or II) and treatment: G1- Ib, enalapril; G2 – Ib losartan; G3 enlapril + furosemida; G4 losartan + furosemida; G5 enalapril + losartan. Physical examination, electrocardiographic examinations and determination of blood pressure were performed on day 0, 14, 28 and 56 after the begging of treatment, whereas radiographic and echocardiogram just at the day 0 and 56. Data was submitted to analysis of variance with repeated measures. there was no difference (P> 0.05) when comparing the dogs treated with enalapril and losartan and its combinations within the classes Ib and II for echoDopplercardiographic, electrocardiographic and radiographic parameters. The measuring radiographic Vertebral Heart Size was significant (P <0.05) decreased this variable to the time factor, of all groups and the P-wave and the QRS complex duration (P <0.05). It was concluded that losartan has a similar effect of enalapril in the initial treatment (first 56 days) in dogs with DMMVD class Ib and II of the CHF
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Wathen, Christopher George. "Studies of the cardiovascular effects of inotropic agents and vasodilators on the pulmonary and systemic circulation in man." Thesis, University of Edinburgh, 1988. http://hdl.handle.net/1842/27032.
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Gomez, Ortiz Edna Mireya. "Avaliação cardíaca de cães com degeneração valvar mixomatosa durante o emprego de enalapril, losartana, furosemida e suas combinações /." Jaboticabal : [s.n.], 2011. http://hdl.handle.net/11449/89198.
Full textAbstract:
Orientador: Aparecido Antonio CamachoBanca: Mirela Tinucci Costa
Banca: Wagner Luis Ferreira
Resumo: A degeneração valvar mixomatosa (DVM) é a afecção cardíaca mais comum em cães. O tratamento da insuficiência cardíaca congestiva (ICC) decorrente da DVM baseia-se no uso de inibidores da enzima conversora de angiotensina - ECA. Antagonistas dos receptores de angiotensina II - ARAs promovem o bloqueio completo da angiotensina II, e são usados no tratamento de ICC em humanos, mas não é comum em cães. O objetivo desta pesquisa foi comparar as respostas clínicas de cães com DVM tratados com enalapril- ECA, losartana -ARAs, furosemida - diurético de alça ou suas combinações. Vinte e nove cães foram distribuídos em cinco grupos dependendo da classe de ICC (Ib ou II) e do tratamento: G1 - Ib, enalapril; G2 - Ib, losartana; G3 - II, enalapril + furosemida; G4 - II, losartana + furosemida; G5- II, enalapril + losartana. Realizou-se exame físico, e determinaramse medidas eletrocardiográficas e pressão arterial nos dias 0, 14, 28 e 56 após início dos tratamentos. Medida radiográfica - Vertebral Heart Size, e variáveis ecodopplercardiográficas obtiveram-se nos dias 0 e 56. Submeteram-se os dados a analise de variância com medidas repetidas. Não houve diferenças (P>0,05) nas variáveis ecodopplercardiográficas, eletrocardiográficas e radiográficas quando comparados cães tratados com enalapril, losartana e suas combinações, tanto com ICC da classe Ib quanto da II. Nos cães de todos os grupos houve diminuição (P> 0,05), a través do tempo, da Vertebral Heart Size e redução (P> 0,05) da duração da onda P e do complexo QRS. Concluiu-se que losartana atua de forma similar ao enalapril no tratamento inicial (primeiros 56 dias) de cães com DVM em fases Ib e II da ICC
Abstract: Degenerative myxomatous mitral valve disease (DMMVD) is the most common cardiac disease in dogs. The treatment of congestive heart failure (CHF) due to DMMVD is based, among others, on the use of vasodilators, like angiotensin converting enzyme (ACE) inhibitors. Recently, other vasodilators such as angiotensin II receptor antagonists (ARAs) have been used in humans with CHF and have promoted a complete blockage of angiotensin II, but is not common in dogs. Thus, the purpose of this investigation was to compare clinical outcomes of enalapril- ACA , losartan - ARAs, furosemide loop diuretic and its combinations in the treatment of CHF in dogs with DMMVD. For this, 29 dogs were distributed into five groups regardless of class of CHF (Ib or II) and treatment: G1- Ib, enalapril; G2 - Ib losartan; G3 enlapril + furosemida; G4 losartan + furosemida; G5 enalapril + losartan. Physical examination, electrocardiographic examinations and determination of blood pressure were performed on day 0, 14, 28 and 56 after the begging of treatment, whereas radiographic and echocardiogram just at the day 0 and 56. Data was submitted to analysis of variance with repeated measures. there was no difference (P> 0.05) when comparing the dogs treated with enalapril and losartan and its combinations within the classes Ib and II for echoDopplercardiographic, electrocardiographic and radiographic parameters. The measuring radiographic Vertebral Heart Size was significant (P <0.05) decreased this variable to the time factor, of all groups and the P-wave and the QRS complex duration (P <0.05). It was concluded that losartan has a similar effect of enalapril in the initial treatment (first 56 days) in dogs with DMMVD class Ib and II of the CHF
Mestre
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Kulczynska, Agnieszka. "N-hydroxyguanidines and related compounds as nitric oxide donors." Thesis, University of St Andrews, 2009. http://hdl.handle.net/10023/957.
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The design of new, improved NO-donor drugs is an important pharmacological objective due to the biological importance of nitric oxide. N-Hydroxyguanidines represent a useful class of NO donors where the mechanism of action is based on the biosynthetic pathway for NO. Thirty new N-arylalkyl-N’-hydroxyguanidines were synthesized and their vasodilatation activity examined by myography in rat aortic rings. The observed relaxations were reversed by ODQ, which is an inhibitor of the guanylate cyclase, implying that this was an NO dependent vasodilatation. The most active compounds were also tested in the isolated perfused kidney (IPK) giving the vasodilatation properties. Preliminary results indicated that N-phenyl-N’- hydroxyguanidine showed the best pharmacological profile with EC₅₀= 19.9 μM and ca. 100% reversibility with ODQ. A series of N-phenylalkyl-N’-hydroxyguanidines were synthesised. NO donor activity was found to be fairly constant up to three methylene groups, and then decreased. Substitutions in the benzene ring of N-phenylethyl-N’-hydroxyguanidine demonstrated that various electron-withdrawing and electron-donating groups in the para position did not significantly affect the NO donor activity of this series of analogues. The nitro and trifluoromethyl substituted compounds gave the best biological profiles. Additionally, a novel heterocyclic, N–furfuryl-N’–hydroxyguanidine possessed very promising vasodilatation properties. In general, almost all the N-arylalkyl-N’-hydroxyguanidines behaved as potent NO donors in the rat aorta assay. In order to establish the influence of the free NH₂ group in the hydroxyguanidine functionality on the vasodilatation properties, N,N-dimethyl and N-methyl-N’- hydroxyguanidines were successfully synthesised. Unfortunately, they have not been tested yet in the biological assay. However, their NMR spectra showed some unusual features and their detailed analysis and X-ray data are presented herein. In addition a series of hydroxamic acids was synthesised and the NO donor activity investigated using the same biological methodology. It was found that the 3-phenylpropionohydroxamic acid was the most potent compound with EC₅₀ = 6 μM and ODQ = 96%. However, behavior in the IPK indicated that hydroxamic acids did not undergo the same biological pathway as in the rat aorta. Two different types of enzyme-activated pro-drugs were designed using N-hydroxyguanidines as the NO donating molecule. Synthetic studies towards these targets were carried out using various synthetic approaches. The desired molecules have not yet been synthesised but the chemistry explored so far has indicated potentially more successful approaches that could be attempted.
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Lunkes, Daniéle Sausen. "Interferência de vasodilatadores na hidrólise de nucleotídeos da adenina em plaquetas de pacientes hipertensos." Universidade Federal de Santa Maria, 2009. http://repositorio.ufsm.br/handle/1/11097.
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The thrombogenic process that affects the hypertensive patient is associated
with regulatory mechanisms present in the vascular endothelium. These mechanisms
involve the release of a endothelium-derived relaxing factor, ectonucleotidases and
calcium ions. Considering that vasodilators act both on blood pressure and on
homeostasis, we evaluated the interference of different vasodilators on platelet
NTPDase activity in hypertensive and healthy patients, with the objective of verifying
patient sensitivity to vasodilators. In addition, the kinetic behavior of NTPDase was
determined in the presence of the vasodilator that showed the greatest inhibitory
influence. The results showed a decrease in NTPDase activity in the presence of
arginine (0.025 mM 3.0 mM), sodium nitroprusside (0.01 mM 2.0 mM) and
hydralazine (20.0 μM 90.0 μM), when tested for ATP and ADP substrate. However,
the hydrolysis of ATP and ADP substrates increased when tested in the presence of
arginine in the control group. No effects on enzyme activities were observed when
pharmacological doses of captopril were tested in vitro. Kinetic behavior studies were
estimated in the presence of sodium nitroprusside, which caused a mixed inhibition.
The Km values increased and Vmax decreased with increasing sodium nitroprusside
concentrations. The IC50 values were 3.66 mM and 2.64 mM (control group) and
2.08 mM and 3.15 mM (hypertensive group) for ATP and ADP, respectively. The Ki
values obtained were 0.345 mM and 2.00 mM for the control group and 0.167mM
and 0.325 mM for the hypertensive group, using ATP and ADP as substrate,
respectively. In conclusion, based on these results it is possible to speculate that
there is an interaction between vasodilators, donors of nitric oxide, and the inhibition
of adenine nucleotide hydrolysis on platelets of hipertensive patients.O processo trombogênico que afeta os pacientes hipertensos está associado com mecanismos regulatórios presentes no endotélio vascular. Esses mecanismos envolvem o fator de relaxamento do endotélio, as ectonucleotidases e íons cálcio. Considerando que os vasodilatadores atuam em ambos, na pressão sangüínea e na homeostase, foi avaliada a interferência de diferentes vasodilatadores na atividade da NTPDase de plaquetas de hipertensos e pacientes saudáveis, com o objetivo de verificar a sensibilidade destes pacientes aos vasodilatadores. Além disso, foi determinado o comportamento cinético da NTPDase na presença do vasodilatador que apresentou maior influência inibitória. Os resultados mostraram uma diminuição na atividade da NTPDase na presença de arginina (0,025 mM 3.0 mM), nitroprussiato de sódio (0,01 2,0 mM) e hidralazina (20,0 μM 90,0 μM), quando testada para os substratos ATP e ADP em plaquetas do grupo hipertensos. Porém, a hidrólise dos substratos ATP e ADP aumentou quando testado na presença de arginina no grupo controle. Nenhum efeito foi observado sobre a atividade da enzima quando doses farmacológicas de captopril foram testadas in vitro. Estudos do comportamento cinético foram realizados na presença de nitroprussiato de sódio, o qual causou uma inibição mista. Os valores de Km aumentaram e os de Vmax diminuíram com o aumento da concentração de nitroprussiato de sódio. Os valores de IC50 foram 3,66 mM e 2,64 mM (grupo controle) e 2,08 mM e 3,15 mM (grupo hipertenso) para ATP e ADP, respectivamente. Os valores de Ki obtidos foram 0,167 mM e 0,325 mM para o grupo hipertensos, usando ATP e ADP como substrato, respectivamente. Contudo, baseado nos resultados encontrados, é possível sugerir que existe uma interação entre vasodilatadores, doadores de óxido nítrico e a inibição da hidrólise de nucleotídeos da adenina em plaquetas de pacientes hipertensos.
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Mauro, Maria Fernanda Zuliani. "Análise volumétrica da hiperplasia intimal intra-stent farmacológico em pacientes diabéticos tratados com ou sem cilostazol." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/98/98131/tde-04102013-090756/.
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Fundamentos: Ensaios prévios reunindo pacientes em series consecutivas ou randomicas sem cegamento evidenciaram beneficio da adição do cilostozol à terapia antiplaquetária em diabéticos submetidos ao implante de stents coronários farmacológicos com redução nas taxas de reestenose binária, perda tardia intra-stent e revascularização tardia da lesão alvo. Objetivos: O objetivo primário deste estudo foi verificar se a adição do cilostazol à dupla terapia antiplaquetária, proporcionaria uma redução adicional da hiperplasia intimal em diabéticos após o implante de stent farmacológico, mensurada por meio do cálculo do volume de obstrução pelo ultrassom intracoronário 9 meses após o procedimento índice. Os objetivos secundários foram aferir a angiografia quantitativa do vaso alvo e ocorrência de eventos cardíacos adversos graves (óbito, infarto do miocárdio não fatal e necessidade de nova revascularização da lesão-alvo) aos 30 dias, 9 meses e 1 ano. Casuística e métodos: Estudo prospectivo, unicêntrico, randomizado, duplo cego, reunindo 133 pacientes diabéticos, comparando pacientes que receberam cilostazol (Grupo 1, n= 65 ) versus placebo (Grupo 2, n= 68), submetidos a implante de stent coronário com liberação de zotarolimus em artéria coronária nativa com estenose maior ou igual a 50% e diâmetro de referência igual ou superior a 2,0 mm (avaliação visual), com reestudo angiográfico e análise ultrassonográfica aos 9 meses. Resultados: Os 2 grupos foram similares nas características clínicas, angiográficas e técnicas, exceto na evidencia de maior incidência de hipertensão arterial no grupo 2 (81,5% vs 94,1%, p=0,026) assim como nos diâmetros dos stents coronários utilizados, significativamente menores no grupo 1 (2,78 mm vs 2,96 mm, p<0,001). O calculo do volume de obstrução intimal por meio do ultrassom intracoronário aos 9 meses foi similar entre os grupos (33,2% vs 35,1%, p=0,069), assim como as taxas de eventos cardíacos adversos graves (12,3% vs 8,8%, p= 0,811), trombose de stent (1,5% versus 0,75%, p= 0,237), reestenose binária intra-sent (9,8% vs 6,8%, p= 0,988), perda tardia intra-stent (0,60 vs 0,64, p=0,300) e no segmento ( 0,57 vs 0,58, p= 0,387). Conclusões: A adição do cilostazol à dupla terapia antiplaquetária com ácido acetilsalicílico e clopidogrel em pacientes diabéticos submetidos à implante de stent com zotarolimus, não reduziu eventos cardíacos adversos graves ou o porcentual de hiperplasia intimal intra-stent mensurado pela análise volumétrica do ultrassom intracoronário.Background: Previous trials with assembled patients in consecutive or random series without blindness offered evidence of the benefit adding cilostazol to the antiplatelet therapy in diabetic patients undergoing drug-eluting stents coronary implantation, with reduction in binary restenosis rates, in-stent late loss and late target lesion revascularization. Objectives: The primary objective of this study was to determine whether the addition of cilostazol to the dual antiplatelet therapy would provide an additional intimal hyperplasia reduction in diabetic patients after drug-eluting stents implantation, measured by calculating the obstruction volume through the intravascular ultrasound 9 months after the index procedure. Secondary objectives were to assess the target vessel quantitative angiography and the occurrence of serious adverse cardiac events (death, nonfatal myocardial infarction and need for a target lesion revascularization) at 30 days, 9 months and 1 year. Methods: Prospective, single center, randomized, double blinded study, gathering 133 diabetic patients, comparing who received cilostazol (Group 1, n= 65) versus placebo (Group 2, n= 68), undergoing coronary stenting, with the releasing of zotarolimus in a native coronary artery with stenosis greater than or equal to 50% and reference diameter equal to or greater than 2.0 mm (visual assessment) with the intravascularultrasound and angiographic restudy at 9 months. Results: Both groups were similar in clinical, angiographic and technical characteristics, except for a higher incidence of arterial hypertension in group 2 (81,5% vs 94,1%, p=0,026) as well as significantly lower coronary stents diameters in group 1 (2,78 mm vs 2,96 mm, p<0,001). The intimal obstruction volume calculated by the intravascularultrasound at 9 months was similar between the groups (33,2% vs 35,1%, p=0,069), as well as the rates of major adverse cardiac events (12,3% vs 8,8%, p= 0,811), stent thrombosis (1,5% versus 0,75%, p= 0,237), in-stent binary restenosis (9,8% vs 6,8%, p= 0,988), in stent late loss (0,60 vs 0,64, p=0,300) and at the segment ( 0,57 vs 0,58, p= 0,387). Conclusions: The addition of cilostazol to the dual antiplatelet therapy with acetylsalicylate acid and clopidogrel, in diabetic patients undergoing stent implantation with zotarolimus did not reduce major adverse cardiac events nor the percentage of intra-stent intimal hyperplasia measured by the intravascularultrasound volumetric analysis.
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Cunha, Patrícia Santos. "Efeito vasorelaxante dos isômeros (+) e (-)-linalol em artéria mesentérica de rato." Pós-Graduação em Ciências Fisiológicas, 2013. https://ri.ufs.br/handle/riufs/3972.
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Linalool is a monoterpene can be biosynthesized by some plants in the racemic form, ( })-linalool, or in the form of enantiomers, (+)-linalool or (-)-linalool. The evaluation the activity of pure isomers has become important in the discovery of new drugs with improved therapeutic potential and a lower rate of adverse effects. So, the objective of the present study was to evaluate the vasorelaxant action induced by the enantiomers, (+) and (-)-linalool in rat superior mesenteric artery, besides seeks to elucidate the mechanisms of action involved in this effect. For both, male Wistar rats (200 . 300 g) were euthanized by exsanguination under anesthesia and superior mesenteric artery was removed. Rings were obtained (1-2 mm) this artery, and were mounted in organ baths containing 10 mL of Tyrode fs solution at 37 C and gassed with carbogen. For isometric tension recordings, each ring was suspended by cotton thread fixed in a force transducer connected to an acquisition system. In rings with functional endothelium pre-contracted with 10 ÊL of phenylephrine, both enantiomers were able to induce significant concentration-dependent vasorelaxation. Such as the effect presented by the (-)-linalool (Emax = 75 } 3%, n = 6) were higher than those for the (+)-linalool (Emax = 41 } 3%, n = 4), sought to evaluate the mechanism of action involved in their action vasorelaxant. In rings without functional endothelium, the vasorelaxation induced by (-)-linalool was significantly attenuated compared to the condition where the rings with functional endothelium were pre-contracted with phenylephrine (Emax = 55 } 1.5%, n = 5). Similar results were obtained after incubation with 10-8 M of atropine, an antagonist of muscarinic receptors (Emax = 50 } 5 %; n = 5); or with 10-4 M of L-NAME, an inhibitor of NO synthesis (Emax = 57 } 5 %; n = 6); or with 30 ÊM of hydroxocobalamin, a NO scavenger (Emax = 45 } 5 %; n = 6). In rings without functional endothelium incubated with 1 mM TEA, a blocker of non-selective K+ channels, the vasorelaxation induced by (-)-linalool had not changed significantly (Emax = 70 } 4 %; n = 4). However, in endothelium-denuded rings pre-contracted with KCl 80 mM, the oil-induced relaxation was significantly higher than that obtained without functional endothelium in rings pre-contracted with phenylephrine (Emax = 92 } 2 %; n = 5). In addition, isolated concentrations of (-)-linalool significantly reduced the contractions induced by CaCl2 (10-6 . 10-2 M) or by Na3VO4 (10-5 . 3 x 10-2 M), a non-selective inhibitor of protein tyrosine phosphatases. These results suggest that the effects induced by linalool occur mainly by the action of one of its isomers, the (-)-linalool. This isomer produces an effect vasorelaxant in rat superior mesenteric artery which is in part, dependent on the endothelium which is given by the activation of muscarinic receptors and the NO release. Furthermore, the endothelium-independent vasorelaxation is due to inhibition of calcium channel voltage-sensitive and involves the sensitization of the contractile machinery in vascular smooth muscle.Linalol e um monoterpeno que pode ser biossintetizado por algumas plantas na forma racemica, ( })-linalol, ou na forma de enantiomeros, (+)-linalol ou (-)-linalol. A avaliacao da atividade dos isomeros puros tem tornado-se importante para a descoberta de novas drogas com melhor potencial terapeutico e menor indice de efeitos colaterais. Assim, o objetivo do presente estudo foi avaliar a acao vasorelaxante induzida pelos enantiomeros, (+) e (-)-linalol em arteria mesenterica superior de rato, alem de buscar elucidar os mecanismos envolvidos neste efeito. Para tanto, ratos Wistar machos (200 . 300 g) foram sacrificados por dessangramento sob anestesia e a arteria mesenterica superior foi removida. Desta arteria foram obtidos aneis (1-2 mm) que foram mantidos em cubas para orgao isolado contendo 10 mL de solucao nutritiva de Tyrode a 37 oC e gaseificada com carbogenio. Para o registro das contracoes isometricas, cada anel foi suspenso por linha de algodao fixada a um transdutor de forca conectado a um sistema de aquisicao de dados. Em aneis com endotelio funcional pre-contraidos com 10 ÊM fenilefrina, ambos enantiomeros foram capazes de induzir vasorelaxamento significativo dependente da concentracao. Como o efeito apresentado pelo (-)-linalol (Emax = 75 } 3 %; n = 6) foi maior que aquele apresentado pelo (+)-linalol (Emax = 41 } 3 %; n = 4), buscou-se avaliar o mecanismo de acao envolvido em sua acao vasorelaxante. Em aneis sem endotelio funcional, o vasorelaxamento induzido pelo (-)-linalol foi significativamente atenuado em relacao a condicao onde os aneis com endotelio funcional foram pre-contraidos com fenilefrina (Emax = 55 } 1,5 %; n = 5). Resultados semelhantes foram obtidos apos incubacao com 10-8 M de atropina, um antagonista de receptores muscarinicos (Emax = 50 } 5 %; n = 5); ou 10-4 M de L-NAME, um inibidor da sintese de NO (Emax = 57 } 5 %; n = 6); ou 30 ÊM de hidroxocobalamina, um sequestrador de NO (Emax = 45 } 5 %; n = 6). Em aneis sem endotelio funcional pre-incubados com 1 mM de TEA, um bloqueador nao seletivo de canais para K+, o vasorelaxamento induzido pelo (-)-linalol nao foi alterado significativamente (Emax = 70 } 4 %; n = 4). Porem, em aneis sem endotelio funcional pre-contraidos com KCl 80 mM, o vasorelaxamento induzido pelo oleo foi significativamente maior que aquele obtido em aneis sem endotelio funcional pre-contraidos com fenilefrina (Emax = 92 } 2 %; n = 5). Alem disso, concentracoes isoladas de (-)-linalol foram capazes de antagonizar contracoes induzidas por CaCl2 (10-6 . 10-2 M) e Na3VO4 (10-5 . 3 x 10-2 M), um inibidor nao-seletivo de proteinas tirosina-fosfatases. Estes resultados sugerem que os efeitos induzidos pelo linalol ocorrem, principalmente, pela acao de um de seus isomeros, o (-)-linalol. Este isomero produz um efeito vasorelaxante em arteria mesenterica superior de rato que e em parte, dependente do endotelio, o qual se da pela ativacao de receptores muscarinicos e pela liberacao de NO. Alem disso, o vasorelaxamento independente do endotelio e decorrente da inibicao dos canais para calcio sensiveis a voltagem e envolve a sensibilizacao da maquinaria contratil na musculatura lisa vascular.
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Martorana, M. G. "Vasodilator aspects of some cardiac inotropic agents." Thesis, University of Strathclyde, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.372098.
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McGinn, Jennifer Sarah. "The vasodilatory and antioxidant activities of polyphenolic substances." Thesis, University of Glasgow, 2002. http://theses.gla.ac.uk/1583/.
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This project was designed to determine the effect of a wide range of grape and tea based extracts and green tea catechins on vascular tension in vitro, further determine the relationship between their vasodilatory and antioxidant activities and identify the major polyphenols present in green and black tea. Grape and tea based extracts were examined for their vasodilator activity in vitro using standard organ bath pharmacology. All extracts evoked biphasic concentration-dependent relaxation in rabbit aortic vessels. Grape based extracts were significantly better vasodilators than tea based extracts. Previous work by others has shown that grape based products induce vascular relaxation via nitric oxide (NO) and endothelium-dependent mechanisms. This study demonstrated that a range of grape based extracts induced vasorelaxation responses via complex mechanisms including endothelium-dependent and independent mechanisms via vasodilating prostaglandins by way of prostacyclin and endothelial NO production. Tea based extracts on the other hand, induced vasorelaxation via the combined interactions of vasodilating endothelium-dependent prostaglandins. The relationship between the vasodilation capacity, antioxidant activity, based on the reduction of the free Fremy's radical and ferric reducing power, and total phenolic content of each extract was also determined. In general, a significant inverse correlation was identified between the vasodilator abilities of the grape and tea extracts in vitro and their antioxidants activities. This study demonstrates that grape and tea based extracts induce vasorelaxation in isolated rabbit aortic vessels and are effective antioxidants in vitro, within a concentration range that may be reached in vivo by moderate wine and tea consumption. The results presented here also indicate that consumption of green tea may have greater benefits than consumption of black tea in terms of their vasodilatory activity and antioxidant capacity in vitro.
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Reis, Lais Vissotto Garchet Santos. "Efeito da cafeína na detecção de isquemia à cintilografia de perfusão miocárdica associada ao estresse com adenosina." Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/5/5131/tde-01022011-162926/.
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A utilização da cintilografia de perfusão miocárdica (CPM) estava limitada a pacientes que podiam realizar algum tipo de exercício, para ampliarmos a disponibilidade clínica da CPM, vários protocolos com estresses farmacológicos foram desenvolvidos. A adenosina fármaco amplamente utilizado, potente vasodilatador coronariano, apresenta uma importante interação com outras substâncias que anatagonizam seus efeitos, o dipiridamol, alimentos com cafeína e derivados de xantinas. O tempo de suspensão de cafeína da dieta para o uso exógeno da adenosina na realização da CPM ainda não está definido. Para testar essa hipótese avaliamos a influência da abstinência de cafeína em 24h, 12h e 1h, através de sua dosagem sérica, antes do estresse farmacológico com adenosina e sua possível repercussão nas imagens da CPM e o efeito vasodilatador no sistema cardiovascular. Definimos como objetivo primário: comparar a presença e a extensão dos defeitos reversíveis da CPM verificados em pacientes com abstinência de café por 24 horas (E1) com as imagens da randomização com 1 hora e 12 horas (E2) sem cafeína e como objetivos secundários: avaliar a presença e intensidade dos paraefeitos, comportamento da frequência cardíaca e da pressão arterial sistêmica. Foram submetidos ao estresse farmacológico com adenosina 194 pacientes para a realização da CPM, dos quais 43 pacientes preencheram os critérios para a randomização (defeitos perfusionais transitórios na CPM com adenosina). Excluímos seis pacientes (13,9%), três (6,9%) se recusaram a realizar a fase da randomização e os outros três (6,9%) nos quais não houve consenso entre os observadores em relação aos defeitos de perfusionais transitórios. A média de idade dos 37 pacientes analisados foi de 61,4 ± 8,3 anos, sendo 21 pacientes do sexo masculino (56,8%). Na avaliação das imagens da CPM, não houve diferença entre as imagens obtidas no grupo E1 comparadas as imagens de 1 (2,0 ± 1,5) hora ou 12 (12,6 ± 3,1) horas sem cafeína (E2). As médias de cafeína sérica encontradas foram de 0,14 ± 0,17 mg/l no grupo E1 do E2 de 1 hora e 0,13 ± 0,24 mg/l no grupo E1 do E2 de 12 horas, na randomização de 1 hora de 1,97± 0,83 mg/l e de 12 horas de 1,51 ± 1,46 mg/l (E1 vs. E2: p < 0,001). Em relação à presença dos paraefeitos, ocorreram em 31 pacientes (83,7%) e os mais freqüentes foram: dor precordial atípica, cansaço e dor em região cervical. Não foram observadas diferenças em relação às freqüências absolutas e relativas na ocorrência de paraefeitos entre os grupos. A intensidade dos paraefeitos foi verificada através de análise subjetiva comparando os sintomas em relação aos exames. Notou-se que em 22 pacientes (59,4%), caracterizaram o estudo randomizado como bem melhor, ou melhor, que o de 24 horas. A pressão arterial sistêmica e a freqüência cardíaca também não apresentaram diferenças entre os grupos. Conclusões: Os resultados permitem inferir que o uso da cafeína ingerida 2 horas antes da realização da CPM com adenosina foi eficaz e segura, pois apesar da modificação da resposta vasodilatadora máxima alcançada, traduzida pela melhor tolerância do exame realizado com menos tempo de ausência de cafeína na dieta, não modificou o resultado final da CPMMyocardial perfusion imaging (MPI) in the past was only available to patients who were able to perform some type of exercise. Many protocols were developed with pharmacologic stress in order to enlarge the clinical availability of myocardial perfusion imaging (MPI). Adenosine is widely used and a potent coronary vasodilator, exhibits a significant interaction with other substances which antagonize its effects, such as dipyridamole, food products containing caffeine and xanthine derivatives. We found no clear consensus as to the time between caffeine ingestion and a cardiovascular adenosine stress test. To test this hypothesis we evaluated the influence of 24-hour, 12-hour and 1-hour caffeine abstinence, by assessing plasma caffeine levels before adenosine pharmacological stress, the possible repercussions on MPI images and vasodilatory effects on the cardiovascular system. The primary endpoint was to compare the presence and extent of reversible myocardial perfusion defects found in patients with 24-hour abstinence from coffee (E1), with images from patients randomized to 1-hour or 12-hour caffeine abstinence (E2). As secondary endpoints we evaluated the presence and intensity of paraeffects, as well as heart rate and systemic arterial blood pressure behavior. For this purpose, 194 patients underwent pharmacological stress with adenosine for MPI, 43 of whom fulfilled criteria for randomization (patients with transient perfusion defects detected on adenosine MPI). Six patients were excluded (13.9%), three patients (6.9%) who refused to undergo randomization, and other three (6.9%) in whom the observers could not reach consensus regarding transient perfusion defects. Mean age for the 37 patients analyzed was 61.4 ± 8.3 years, 21 patients male (56.8%). In the evaluation of myocardial perfusion images, no differences were detected between images obtained in the 24-hour E1 arm, and those from 1 (2.0 ± 1.5) hour or 12 (12.6 ± 3.1) hours randomization E2. Mean plasma caffeine level was 0.14 ± 0.17 mg/l in group E1 of the 1-hour arm E2, and 0.13 ± 0.24 mg/l in group (E1) of the 12-hour arm (E2), respectively, compared with 1.97± 0.83 mg/l, in the 1-hour, and 1.51 ± 1.46 mg/l, in the 12-hour (E2) randomized arms (E1 vs. E2: p < 0.001). In the 31 patients (83.7%) with presence of paraeffects, the most frequent were: atypical precordial pain, tiredness and pain on cervical area. There were no differences in the absolute and relative frequency in the occurrence of paraeffects between groups. However, with respect to the intensity of pareffects, a subjective analysis was undertaken, comparing symptoms of two exams. which resulted in 22 patients (59.4%) ranking the randomized study a lot better, or better than the 24-hour one. The systemic blood pressure and the heart rate behavior also did not reveal any significant differences between groups. Conclusions: The results may imply that the use of caffeine ingested 2 hours prior to the CPM with adenosine was effective and safe, for despite the change in maximal vasodilator response achieved, manifested by better tolerance of the examination with less time in the absence of caffeine in the diet, did not change the final result of the CPM
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Shi, Yun. "KATP Channel Phosphorylation: Mechanisms and Contribution to Vascular Tone Regulation by Vasodilating and Vasoconstricting Hormones and Neurotransmitters." unrestricted, 2007. http://etd.gsu.edu/theses/available/etd-11302007-150810/.
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Thesis (Ph. D.)--Georgia State University, 2007.Title from file title page. Chun Jiang, committee chair; Teryl Frey, Deborah Baro, Delon Barfuss, committee members. Electronic text (168 p. : ill. (some col.)) : digital, PDF file. Description based on contents viewed Jan. 30, 2008. Includes bibliographical references (p. 146-151).
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Drake, W. M. "Desensitisation of calcitonin gene-related peptide of adrenomedullin receptors in vascular smooth muscle of SK-N-MC cells." Thesis, University of Oxford, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.275192.
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Barker, Diana May. "Investigations of the vasodilator actions of corticotrophin-releasing factor." Thesis, Queen Mary, University of London, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.299182.
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Abu-Kishk, Rabee Awni. "Vasodilator mechanisms and the intracellular control of renin secretion." Thesis, University of Southampton, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.292931.
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Stride, Ann Elizabeth. "Mechanisms underlying the metabolic and vasodilator effects of insulin." Thesis, University of Birmingham, 2013. http://etheses.bham.ac.uk//id/eprint/4297/.
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Insulin causes uptake of glucose into cells and also causes increases in skeletal muscle blood flow by vasodilatation. In order for insulin to act at receptors on the skeletal muscle membrane, it must move through the capillary endothelium. In conditions associated with insulin resistance, insulin-induced glucose uptake and vasodilatation are often blunted and disordered transport across endothelium has been suggested. Firstly, studies were conducted using the hyperinsulinaemic euglycaemic (HE) clamp in rats to assess the relationship between insulin-induced muscle vasodilatation and glucose uptake into skeletal muscle. Insulin-induced vasodilatation was abolished by nitric oxide (NO) synthase inhibition in Wistar rats, implicating NO. Nutritional status and hence availability of glucose also affected vasodilatation in Wistar rats, leading to the proposal that vasodilatation was linked to glucose metabolism. Vasodilator response to insulin was significantly higher in lean versus obese Zucker rats. Nicotinic acid (NAc) did not decrease plasma FFA concentrations versus HE clamp, nevertheless, vasodilator response and glucose uptake were enhanced in lean and obese rats by some mechanism other than lowering FFA. Optimisation of the microdialysis technique allowed measurement, for the first time, of interstitial insulin concentrations in lean and obese Zucker rats and showed a significant difference under basal conditions.
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Love, Alastair I. "Factors affecting nerve regeneration and function in experimental diabetes." Thesis, University of Aberdeen, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.241877.
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Rats with streptozotocin-induced diabetes exhibit both a reduction in nerve conduction velocity (NCV) and an impaired regenerative response after nerve injury. Nerve blood flow is also reduced in diabetic rats. Vasodilator treatment normalized the deficit in maximum regeneration distance after nerve injury. This strongly suggests a role for endoneurial hypoxia in the impaired regenerative response associated with diabetes. Inhibition of polyol pathway hyperactivity in diabetic rats corrects the deficit in nerve regeneration. Compensation for impaired essential fatty acid metabolism with evening primrose oil treatment had no significant effect on nerve regeneration, but corrected NCV. These findings implicate these two hyperglycemia-related metabolic disturbances in the development of diabetic nerve dysfunction. Levels of oxidative stress are increased in diabetic rats. It was demonstrated that various treatments which act to decrease levels of oxidative stress corrected both the deficit in nerve regeneration and the reduction in NCV found in diabetic rats. It is suggested that an increase in oxidative stress contributes towards nerve dysfunction in diabetes. Feeding non-diabetic rats a 40% galactose diet causes an increase in polyol pathway activity. These animals exhibited similar deficits in nerve regeneration and NCV to those seen in diabetic rats. Anti-oxidant treatment improved both nerve regeneration and NCV in galactose-fed animals. These studies give support to the suggestion that nerve dysfunction due to the diabetes-induced increase in polyol pathway activity involves an increase in levels of oxidative stress. Levels of certain growth factors are reduced in diabetic rats. Treatment of diabetic animals with ciliary neurotrophic factor normalized both nerve regeneration and NCV. Brain-derived neurotropic factor treatment improved nerve regeneration but had no significant effect on NCV.
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Al-Hamidi, Abdulaziz Abdullah Abdulrahman. "Purification and characterization of prokallikrein from bovine pancreas." Thesis, University of Essex, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.278522.
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Yang, Yang. "Vascular KATP Channel Modulation by S-Glutathionylation: A Novel Mechanism for Cellular Response to Oxidative Stress." Digital Archive @ GSU, 2011. http://digitalarchive.gsu.edu/biology_diss/97.
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The KATP channels play an important role in the membrane excitability and vascular tone regulation. Previous studies indicate that the function of KATP channels is disrupted in oxidative stress seen in a variety of cardiovascular diseases, while the underlying mechanism remains unclear. Here, we demonstrate S-glutathionylation to be a modulation mechanism underlying the oxidant-mediated vascular KATP channel inhibition, the molecular basis for the channel inhibition and the alleviation of the channel inhibition by vasoactive intestinal peptide (VIP). We found that an exposure of isolated mesenteric rings to H2O2 impaired the KATP channel-mediated vascular dilation. In whole-cell recordings and inside-out patches, micromolar H2O2 or diamide caused a strong inhibition of the vascular KATP channel (Kir6.1/SUR2B) in the presence, but not in the absence, of glutathione (GSH), indicating S-glutathionylation. By co-expressions of Kir6.1 or Kir6.2 with SUR2B subunits, we found that the oxidant sensitivity of the KATP channel relied on the Kir6.1 subunit. Systematic mutational analysis revealed three cysteine residues (Cys43, Cys120 and Cys176) to be important. Among them, Cys176 was prominent, contributing to >80% oxidant sensitivity. Biochemical pull-down assay with biotinylated glutathione ethyl ester (BioGEE) showed that mutations of Cys176 impaired the oxidant-induced incorporation of GSH to the Kir6.1 subunit. Simulation modeling of Kir6.1 S-glutathionylation revealed that after incorporation to residue 176, the GSH moiety occupied a space between slide helix and two transmembrane helices. This prevented the necessary conformational change of the inner helix for channel gating, and retained the channel in its closed state. VIP is a potent vasodilator, and is shown to have protective role against oxidative stress. We found that the channel was strongly augmented by VIP and the channel activation relied on PKA phosphorylation. These results therefore indicate that 1) the vascular KATP channel is strongly inhibited in oxidative stress, 2) S-glutathionylation underlies the oxidant-mediated KATP channel inhibition, 3) Cys176 in the Kir6.1 subunit is the major site for S-glutathionylation, and 4) the Kir6.1/SUR2B channel is activated in a PKA-dependent manner by VIP that has been previously shown to alleviate oxidative stress.
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Crail, Susan Margaret. "Studies of the function and regulation of vasodilator-stimulated phosphoprotein." Thesis, University of Glasgow, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.433088.
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Southerton, J. S. "Studies on the mechanisms of action of some smooth muscle relaxants." Thesis, University of Manchester, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.237287.
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Patel, Hanif M. S. "Studies on the nitrosation of thiols in relation to vasodilatory action." Thesis, Durham University, 1989. http://etheses.dur.ac.uk/6728/.
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A kinetic study of the nitrosation of L-cysteine, L-cysteine methyl and ethyl esters, N-acetyl-L-cysteine and glutathione by isopropyl nitrite in acid solution at 25 C was undertaken. The thiols exhibited identical rate laws and in all cases the observed rate constant was reduced by added isopropyl alcohol. The results were found to be consistent with the mechanism in which a rapid reversible acid-catalysed hydrolysis of isopropyl nitrite occurs to give nitrous acid, which then in its protonated form effects nitrosation. The third-order rate constant for the nitrosation of the thiols by isopropyl nitrite and the equilibrium constant for the formation of isopropyl nitrite were found to be in good agreement with the literature values obtained by direct measurement. A similar kinetic study of the nitrosation of L-cysteine, L-cysteine methyl and ethyl esters, N-acetyl-L-cysteine, thioglycolic acid and glutathione by various alkyl nitrites, in water at 25 C , in the pH range 6-13 was undertaken. The pH dependence of the rate constant is consistent with a mechanism involving a direct nitrosation by alkyl nitrites with the thiolate anion (RS(^-)) of the thiol. A quantitative kinetic analysis yielded macroscopic and microscopic pKa values for RSH ionisation in good agreement with the literature values. One exception is L-cysteine where the microscopic, pKp, value (for NH(_2)RSH → NH(_2)RS(^-)) differs significantly from the literature value. In the case of simple alkyl nitrites (ethyl, isopropyl, isoamyl and t-butyl nitrites) steric effects appear to be the major influence in reactivity whereas electron-withdrawing substituents in the β-position greatly enhanced the rate constant. The results were found to satisfy Taft's equation and thus a correlation between structure and reactivity of the alkyl nitrites with the thiols was established. This work shows that at least in vitro a direct and rapid reaction occurs between alkyl nitrites and thiols at pH values likely to be encountered in vivo. This confirms that such reactions could occur in vivo and could be an important feature of the chain of events occurring during the vasodilatory action of alkyl nitrites. Finally a preliminary investigation of the reaction of glyceryl trinitrate with cysteine, in oxygen and oxygen-free nitrogen atmosphere, in the pH range 6-13 was undertaken. In this case no evidence was found for the formation of S-nitrosocysteine or nitric oxide from glyceryl trinitrate in the presence or absence of cysteine. Thus the results could not confirm the hypothesis that glyceryl trinitrate owes its vasodilatory action to the formation of the intermediate, S-nitrosocysteine, from the reaction of nitric oxide (formed from glyceryl trinitrate) and cysteine.
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Sletten, Nathan Robert. "Effects of high-intensity interval exercise on vasodilator function in children." Thesis, University of British Columbia, 2017. http://hdl.handle.net/2429/62809.
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Purpose: Exercise training can improve vascular function through anti-atherogenic effects on the vascular endothelium, a response which can be discerned following individual bouts of exercise. Although well characterized in adults, the effect of exercise intensity on the acute recovery patterns of vasodilator function is unknown in children. Study Design: Nine children (age = 10.5 ± 1.5 y, 6 girls) completed 1) high-intensity interval exercise (HIIE, six 1-minute sprints at 90% peak power (Wmax), with 1-minute recovery) and 2) moderate-intensity exercise (MIE, 15 minutes at 44% Wmax, total external work-matched to HIIE). Superficial femoral artery (SFA) diameter, blood flow, shear rates, and flow-mediated dilation (FMD) were measured before (Pre), immediately following (Post), and 60 minutes following (Post60) the exercise trials using duplex ultrasound. Results: Baseline diameter increased similarly following both HIIE (Pre 4.25 ± 0.42 mm, Post 4.76 ± 0.42 mm) and MIE (Pre 4.29 ± 0.49 mm, Post 4.62 ± 0.49 mm), returning to pre-exercise values 60 minutes later. Blood flow and antegrade shear rate were increased following HIIE and MIE, but to a greater extent after HIIE (P < 0.05). Retrograde shear rate was attenuated following both exercise conditions, remaining lower 60 minutes after exercise (P’s < 0.001). FMD was attenuated Post compared to Pre following HIIE (Δ -2.8%) and MIE (Δ -2.5%) (P’s < 0.05) and recovered to pre-exercise values with no difference between Post60 and Pre FMD. When FMD was corrected to account for changes in baseline diameter, there was no longer a significant main effect of time (P = 0.34) making the post-exercise nadir in FMD negligible. Conclusions: Acute bouts of external work-matched HIIE or MIE exert a similar impact on shear-mediated conduit artery vasodilation and FMD in children and this is reversible 60 minutes post-exercise. This suggests the mechanisms that govern the acute FMD response in adolescents and adults may be dissimilar in children.Graduate Studies, College of (Okanagan)
Graduate
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Price, Caroline J. "Molecular interactions and cellular functions of the vasodilator stimulated phosphoprotein (VASP)." Thesis, University of Leicester, 2000. http://hdl.handle.net/2381/29350.
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The vasodilator stimulated phosphoprotein (VASP) is associated with focal adhesions, actin microfilaments and regions of highly dynamic membrane activity in cells. VASP binds to the G-actin-binding protein profilin which regulates actin polymerisation. It also binds to the Listeria monocytogenes surface protein Act A and recruits profilin to the bacterial surface, thereby promoting efficient actin polymerisation for movement of the bacteria. It has been postulated that a cellular homologue of the Act A protein may exist which recruits VASP to cell membrane surfaces. Here, binding of VASP to a potential Act A homologue was investigated. It was found that VASP binds to the cytoskeletal protein vinculin via a similar sequence to the VASP-binding domain in Act A. The significance of the interaction of VASP with vinculin and profilin in actin filament assembly at cell membranes was then investigated. Various deletion constructs of VASP were expressed in cells and the effect on F-actin organisation and cortical activity examined. VASP overexpression in cells caused an increase in membrane ruffling activity and this effect was independent of profilin-binding. This suggests that VASP promotes membrane actin filament assembly through an alternative mechanism. Recently it has been shown that VASP is able to nucleate actin filament assembly in vitro, consistent with this theory. Overexpression of VASP also caused the formation of large stress fibres, through a short region in the C-terminus of the protein. A potential interaction of this region was investigated but no ligand identified. It is now known that this region mediates binding and bundling of F-actin. A model is put forward in which VASP bundles and tethers newly-formed actin filaments in nascent focal complexes at the leading edge of cells.
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Turcato, Sally. "The role of cyclic AMP and K⺠channels in mediating vasorelaxation induced by prostacyclin analogues and other Gs-coupled receptors." Thesis, University College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.342235.
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Sadigh, Bita. "Analgetic and algetic effects of adenosine in healthy volunteers and patients with coronary artery disease /." Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-382-5/.
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Stewart, Derek C. "Implementing formulary recommendations in primary care : effect on patient outcomes." Thesis, Robert Gordon University, 1998. http://hdl.handle.net/10059/615.
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This research aimed to measure the effect on health outcomes of implementing selected recommendations of the Grampian Joint Drug Formulary in primary care. Antibiotics used in the treatment of uncomplicated lower urinary tract infections (UTIs), ulcer healing agents and peripheral vasodilators were selected for study, thereby reflecting both acute and chronic prescribing. For the UTI study, 12 randomly selected high and low prescribers of trimethoprim, the recommended agent, each agreed to distribute 20 patient questionnaires. Following a period of 18 months and despite repeated contact with the GPs, only 89/480 (19%) questionnaires had been distributed. Patient response was, however, very high with 80 (90%) questionnaires returned. Health outcome measures identified that trimethoprim resulted in no or mild symptoms in 40/45 (91 %) of patients. These findings must be interpreted with caution due to the low level of questionnaire distribution and thus cannot be extrapolated to the total population of patients. In addition, the poor questionnaire distribution did not permit comparison between trimethoprim and non-recommended therapy. One hundred and eighty four patients receiving repeat prescriptions for ulcer healing agents were identified from one general practice. Therapy in 95 patients did not adhere to formulary recommendations. Changes to therapy were considered inappropriate in 11 patients due to factors such as severe depression and a further 8 were deemed unsuitable for participation for non-clinical reasons. The remaining 76 patients were contacted with 19 (25%) refusing to participate. Fifty seven patients were interviewed using the Glasgow Dyspepsia Severity Score and Short Form 36 (SF-36). Changes in health outcomes were measured for 21 patients where a change in therapy had taken place. These results were difficult to interpret due to the diversity of changes recommended and the lack of data relating to those patients not participating. Work involving peripheral vasodilators aimed to determine the effect on health outcomes of cessation of therapy. Forty five patients receiving these agents in 2 practices were identified, although 8 had not requested a prescription in the previous year. Two further patients were excluded from the study due to cancer and old age. The remaining 35 agreed to be interviewed using the Walking Impairment Questionnaire and SF-36. All patients were subsequently instructed to stop therapy for 2 months, although 6 (17%) refused to follow this instruction, one patient was seriously ill thus was excluded and 3 refused to be reinterviewed. Of the remaining 25 patients, no significant differences were observed in the domains studied. Seventeen patients (68%) expressed no desire to restart therapy, generating considerable savings. These results must be interpreted with caution since those not stopping therapy or refusing re-interview are likely to have responded differently to those completing the study. The measurement of health outcomes following formulary implementation deserves further work.
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Dawes, Matthew. "Drug-induced vasodilation in human forearm resistance vasculature." Thesis, King's College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.342326.
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Gitlin, Jonathan Max. "Endogenous vasodilator pathways : their interactions and relevance to the vascular effects of ATP." Thesis, Imperial College London, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.271969.
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Demoncheaux, Eric Arthur Germain. "Physico-chemical properties of nitrogen monoxide : implication for its role as a vasodilator." Thesis, Anglia Ruskin University, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.264045.
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Coppock, Hedley Alan. "Investigation of the receptors and mechanisms of action of the novel vasodilator peptide, adrenomedullin." Thesis, Imperial College London, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.327028.
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Sugita, Kenichiro, Masato Shibuya, Masakazu Takayasu, Yasukazu Kajita, Shin-ichi Satoh, Yoshio Suzuki, and Hirofumi Oyama. "Role of Nitric Oxide in the Cerebral Vasodilatory Responses to Vasopressin and Oxytocin in Dogs." Thesis, Nature Publishing Group, 1993. http://hdl.handle.net/2237/16711.
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Lovell, Sharon Lynne. "The role of nitric oxide and endothelin in the regulation of pulmonary arterial pressure in man." Thesis, Queen's University Belfast, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.322648.
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Södergren, Anna. "VASODILATORY EFFECTS OF EXOGENOUS NITRIC OXIDE ON THE BROOD PATCH OF THE ZEBRA FINCH (Taeniopygia guttata)." Thesis, Linköping University, Department of Physics, Chemistry and Biology, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-56855.
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In birds like the Zebra finch (Taeniopygia guttata) the female, but not the male develop a brood patch upon incubation of eggs. The brood patch functions to increase heat exchange between the bird and the eggs. Development of the brood patch includes de-feathering, increased vascularization and edema formation. The increased vascularization is due to the development of arteriovenous anastomoses, AVA. The AVA are thermoregulatory vessels involved in cold induced vasodilation, CIVD, demonstrated to occur in the brood patch. Nitric oxide, NO, which is a well known vasodilator is a candidate substance for involvement in CIVD. In this study a NO-generating gel was applied to the brood patch of male and female zebra finches. Vasodilation was found to be markedly larger in females than in males. The larger vasodilation in the female brood patch is probably because NO vasodilate AVA selectively more than any other vessels. The study also investigated whether vasodilation would cause an increase in brood patch temperature. No definite changes in brood patch temperature could be observed and no conclusions could be drawn in the matter.