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1
Plank, David Michael. "Calcium dynamics, β-adrenergic receptor blockade, and cardiac function in failing and non-failing hearts". University of Cincinnati / OhioLINK, 2003. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1053431441.
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2
Plank, David M. "Calcium dynamics, [beta]-adrenergic receptor blockade, and cardiac function in failing and non-failing hearts". Cincinnati, Ohio : University of Cincinnati, 2003. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=ucin1053431441.
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3
Grogan, Shawn Patrick, of Western Sydney Hawkesbury University, Faculty of Environmental Management and Agriculture e School of Agriculture and Rural Development. "Endocrine alteration of meat quality and gene expression in rats and deer". THESIS_FEMA_ARD_Grogan_S.xml, 1998. http://handle.uws.edu.au:8081/1959.7/724.
Testo completoAbstract (sommario):
Stress activates a number of endocrine pathways that alter an animal's physiology in a manner which can result in undesirable meat quality. Animals frequently exhibit meat quality defects, including ecchymosis, at slaughter due to the stress of slaughter. This thesis explores how stress related hormones interact with adrenergic receptors to alter muscle and vascular physiology. Fallow deer were exposed to either a transciptional regulator (hydrocortisone), a beta adrenergic recptor agonist (clenbuterol) or a beta adrenergic receptor antagonist (propranolol). The administration of hydrocortisone resulted in a negative feed-back type reduction in circulating cortisol. Animals treated with propranolol and clenbuterol displayed less severe eccymosis. These results indicated that the beta 2 adrenergic receptor (B2AR) is important in controlling ecchymosis severity. B2AR was also found to be important in mediating vascular dynamics, growth and energy pathways. To investigate how adrenergic receptors alter skeletal muscle gene expression and meat quality, an in vivo wistar rat model was developed in conjunction with in vitro muscle cell (L6) experiments. Gene expression of B2AR, its associated kinase (BARK) and collagen type III, prolyl- 4-hydroxylase (P4Hy) was measured in rat muscle and L6 cells. Following exposure to clenbuterol and hydrocortisone, growth and meat quality were determined. The L6 experiments revealed that gene expression following exposure to hydrocortisone and B2AR ligands paralleled the in vivo rat changes in B2AR, BARK, collagen type III, and P4Hy gene expression. In both L6 and wistar rat models the B2AR and BARK genes are similarly expressed following clenbuterol exposure. Both rats and deer exposed to clenbuterol had significant increases in growth rate and a reduction of intramuscular fat. The B2AR therefore appears to be a major mediator of many interrelated events including energy distribution, growth and vascular response to stress. Habituating animals to stress stimuli may increase their coping ability and improve welfare and meat quality.Doctor of Philosophy (PhD)
4
Grogan, Shawn Patrick. "Endocrine alteration of meat quality and gene expression in rats and deer". Thesis, [Richmond, N.S.W.] : CSIRO Animal Production : School of Agriculture, University of Western Sydney, Hawkesbury, 1998. http://handle.uws.edu.au:8081/1959.7/724.
Testo completoAbstract (sommario):
Stress activates a number of endocrine pathways that alter an animal's physiology in a manner which can result in undesirable meat quality. Animals frequently exhibit meat quality defects, including ecchymosis, at slaughter due to the stress of slaughter. This thesis explores how stress related hormones interact with adrenergic receptors to alter muscle and vascular physiology. Fallow deer were exposed to either a transciptional regulator (hydrocortisone), a beta adrenergic recptor agonist (clenbuterol) or a beta adrenergic receptor antagonist (propranolol). The administration of hydrocortisone resulted in a negative feed-back type reduction in circulating cortisol. Animals treated with propranolol and clenbuterol displayed less severe eccymosis. These results indicated that the beta 2 adrenergic receptor (B2AR) is important in controlling ecchymosis severity. B2AR was also found to be important in mediating vascular dynamics, growth and energy pathways. To investigate how adrenergic receptors alter skeletal muscle gene expression and meat quality, an in vivo wistar rat model was developed in conjunction with in vitro muscle cell (L6) experiments. Gene expression of B2AR, its associated kinase (BARK) and collagen type III, prolyl- 4-hydroxylase (P4Hy) was measured in rat muscle and L6 cells. Following exposure to clenbuterol and hydrocortisone, growth and meat quality were determined. The L6 experiments revealed that gene expression following exposure to hydrocortisone and B2AR ligands paralleled the in vivo rat changes in B2AR, BARK, collagen type III, and P4Hy gene expression. In both L6 and wistar rat models the B2AR and BARK genes are similarly expressed following clenbuterol exposure. Both rats and deer exposed to clenbuterol had significant increases in growth rate and a reduction of intramuscular fat. The B2AR therefore appears to be a major mediator of many interrelated events including energy distribution, growth and vascular response to stress. Habituating animals to stress stimuli may increase their coping ability and improve welfare and meat quality.
5
Bagley, John Sorrell. "The beta adrenergic receptor in septic shock". Thesis, University of Aberdeen, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.305466.
Testo completoAbstract (sommario):
The myocardial depression found during septic shock has been a subject of intense study for many years. Many theories exist as to the precise cause of this condition but in this thesis the role of the β-adrenergic receptor is examined. Some investigators have found reduced response to β-adrenergic stimulation in models of septic shock in animals. This is of interest to the clinician since adrenergic stimulation is a key manipulation in the management of septic shock. An animal model of septic shock was established using a comparatively small dose of Escherichia coli endotoxin infused into the male Sprague-Dawley rat. Heart function and response to isoprenaline, a β1-agonist, were measured in an in vitro organ bath. A reduction in the force of contraction was found together with a shift in the response curve to the right. These findings were associated with an increase in the number of β-receptors in the ventricular tissue from the same hearts, a measurement made using radioligand binding with I125-(-)-Iodocyanopindolol, a β1-antagonist. The finding of more β-receptors in the context of septic shock raises interesting questions discussed in the thesis. When forskolin, a plant alkaloid that stimulates the adenyl cyclase enzyme, was used to stimulate the atria in vitro the same response was found in the endotoxin treated and the normal groups. This is strong evidence that endotoxin causes a myocardial depressant effect mediated prior to adenylcyclase in the β-receptor transduction cascade.
6
Higgins, Thomas John Diatchenko Luda. "Molecular characterization of [beta]2 adrenergic receptor haplotypes". Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2008. http://dc.lib.unc.edu/u?/etd,1602.
Testo completoAbstract (sommario):
Thesis (M.S.)--University of North Carolina at Chapel Hill, 2008.Title from electronic title page (viewed Sep. 16, 2008). "... in partial fulfillment of the requirements for the degree of Master's of Science in the Curriculum in Neurobiology." Discipline: Neurobiology; Department/School: Medicine. On title page, [beta] appers as Greek character and 2 appears in subscript.
7
Vincent, Karla Kristine. "Transactivation of Beta 2 Adrenergic Receptor by Bradykinin type 2 Receptor via heterodimerization". Diss., Georgia Institute of Technology, 2009. http://hdl.handle.net/1853/37117.
Testo completoAbstract (sommario):
Although a long standing convention maintained that G Protein Coupled Receptors (GPCRs) exist in the plasma membrane solely as monomers, substantial work over the last two decades has demonstrated that these ubiquitous receptors can and in many cases, preferentially, exist as homodimers, heterodimers, or higher order oligomers. Often, two GPCRs of the same class heterodimerize; it is less common for two GPCRs of different signaling pathways to interact. The work presented here studied the physical and functional interaction of two GPCRs from discrete classes, the Beta 2 Adrenergic Receptor (β2AR), a Gαs-coupled receptor, and Bradykinin type 2 Receptor (Bk2R), a Gαq coupled receptor. These data show that Bk2R and β2AR are physically coupled when heterologously expressed in Xenopus oocytes, and in pheochromocytoma (PC12) cells and in freshly isolated murine ventricular myocytes, two systems that endogenously express these receptors. This physical coupling led to functional consequences in heterologous and endogenous expression systems, as Bk2R was able to transactivate β2AR signaling via its direct interaction with the receptor. Furthermore, coexpression of Bk2R shifted the dose response curve of β2AR for its selective agonist rightward in Xenopus oocyte electrophysiology experiments, suggesting the presence of Bk2R negatively affected β2AR native pharmacology. Up to thirty minutes of either bradykinin (BK) or isoproterenol exposure did not change the relative amount of Bk2R/β2AR heterodimer in PC12 cells, a rat adrenal medulla tumor cell line that endogenously expresses these receptors. Despite the obvious signaling consequences, the Bk2R/β2AR heterodimer accounted for only 10% of the total β2AR protein detected and 20% of the total Bk2R protein detected. When other Bk2R-specific ligands were also tested to examine the extent of β2AR transactivation, our data showed that both Lys-des-Arg-Bradykinin, a Bk2R partial agonist and NPC 567, a Bk2R antagonist, transactivated β2AR to the same extent as BK. Taken together, our data provide a novel mode of receptor regulation and signaling via Bk2R/β2AR heterodimerization. Because a large percentage of therapeutics target GPCRs, a greater understanding of how a GPCR heterodimer functions could be beneficial for targeting new drugs and refining existing drugs. Understanding the Bk2R/β2AR heterodimer provides a new perspective on the myriad of fucntional consequences that occur when a GPCR is activated.
8
Snyder, Ellen Amanda Flood Patrick M. "[beta]2-adrenergic receptor modulation of macrophage inflammatory mediator production". Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2007. http://dc.lib.unc.edu/u?/etd,1344.
Testo completoAbstract (sommario):
Thesis (M.S.)--University of North Carolina at Chapel Hill, 2007.Title from electronic title page (viewed Apr. 25, 2008). "... in partial fulfillment of the requirements for the degree of Master of Science in the Curriculum of Oral Biology." Discipline: Oral Biology; Department/School: Dentistry. On title page, [beta] appears as Greek character and 2 appears as subscript.
9
Robson, Alice. "In vitro reconstitution and stability of a beta-adrenergic receptor". Thesis, University of Bristol, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.424005.
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10
Zolty, Ronald. "Beta 1 and Alpha 2C adrenergic receptor polymorphisms and response to beta blockers in heart failure patients /". Connect to full text via ProQuest. Limited to UCD Anschutz Medical Campus, 2007.
Cerca il testo completoAbstract (sommario):
Thesis (Ph.D. in Clinical Science) -- University of Colorado Denver, 2007.Typescript. Includes bibliographical references (leaves 130-142). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;
11
Allcock, Stephen M. J. "Interactions between calpain proteases #beta#-adrenergic receptor and skeletal muscle growth". Thesis, University of Nottingham, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.358286.
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12
Clausen, Lisa. "Effects of beta-2 adrenergic receptor agonists in DOK7 congenital myasthenic syndrome". Thesis, University of Oxford, 2015. https://ora.ox.ac.uk/objects/uuid:9360c51b-8497-47ca-bd16-e917a3614a25.
Testo completoAbstract (sommario):
Congenital myasthenic syndromes (CMS) are a rare group of heterogeneous disorders, characterised by compromised neuromuscular transmission and symptoms of fatiguable muscle weakness. CMS is caused by mutations in genes that affect the structure and function of the neuromuscular junction (NMJ). In about 20% of CMS cases, patients have mutations in the gene DOK7; the protein product, DOK7, is crucial for maintaining the dense aggregation of acetylcholine receptor (AChR) clusters at the NMJ. DOK7-CMS patients do not respond to treatment with acetylcholinesterase inhibitors which are the first line treatment for most forms of CMS. Instead, a dramatic response to beta-2 adrenergic receptor (ADRB2) agonists, such as salbutamol, is observed. The aim of this project was to investigate the molecular mechanisms that underlie the beneficial effects of ADRB2 agonists. Firstly, NMJ functioning was modelled in vitro by studying AChR clusters formed on cultured C2C12 mouse myotubes in the presence of WT DOK7. Overexpression of mutant DOK7 led to a significant reduction in the number of AChR clusters, explaining the pathogenic effect of the mutation. Importantly, incubation of myotubes with salbutamol increased the number of AChR clusters and their stability. The results provide the first evidence that ADRB2 agonists directly affect proteins located at the NMJ. However, this disease model suffers from limitations. The rest of the thesis focussed on developing alternative cell culture models to explore the AChR clustering pathway. The first model combined optogenetics and fluorescence lifetime microscopy to study the effects of ADRB2 activation on AChR cluster stability in single live cells. The second used CRISPR/Cas9 genome editing tools to directly introduce Dok7 mutations to the genome of C2C12 cells, thereby overcoming some of the drawbacks associated with DOK7 overexpression. Further manipulations of these novel model systems will be used in the future to examine in more detail the molecular events underlying the pathogenic effects of DOK7 mutations and the mechanisms of ADRB2 agonists.
13
Owens, Helen. "The effect of beta-adrenergic receptor antagonists on the temporal accommodative response". Thesis, Aston University, 1991. http://publications.aston.ac.uk/14611/.
Testo completoAbstract (sommario):
It is well established that the steady-state accommodative response is characterised by temporal changes in lens power having 2 dominant frequency components: a low frequency component (LFC: < 0.6Hz) and a high frequency component (HFC: 1.0-2.2Hz). This thesis investigates various aspects of these microfluctuations of accommodation. The HFC of accommodative fluctuations was shown to be present in central and peripheral lens zones, although the magnitude of the rms of accommodative microfluctuations was found to be reduced in the lens periphery. These findings concur with the proposal that the lens capsule acts as a force distributor, transmitting the tension from the zonules evenly over the whole of the lens surface. An investigation into the correlation between arterial pulse and the HFC of accommodative fluctuations showed that the peak frequency of the HFC was governed by the arterial pulse frequency. It was proposed that the microflucutations comprised a combination of neurological control (LFC) and physiological variations (HFC). The effect of timolol maleate on the steady-state accommodative response for a group of 10 emmetropes showed that timolol reduced significantly the rms of accommodative microfluctuations in treated but not untreated eyes. Consequently, the effect was considered to be locally, rather than systemically induced. The influence of the sympathetic system on within-task measurements of accommodation was examined by recording the accommodative response of 3 subjects to a sinusoidally moving target at 6 temporal frequencies from 0.05Hz to 0.5Hz for 3 drug conditions: saline, timolol and betaxolol.
14
Clausen, Lisa K. J. "Effects of beta-2 adrenergic receptor agonists in DOK7 congenital myasthenic syndromes". Thesis, University of Oxford, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.712079.
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15
Wardle, Robert L. "Functional antagonism between muscarinic receptor and beta-adrenergic receptor agonists in equine trachealis muscle in vitro /". The Ohio State University, 1994. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487858417981441.
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16
Zheng, Lei. "Synthesis and evaluation of a beta-adrenergic receptor ligand: Fluorine-18 labeled fluorocarazolol". Case Western Reserve University School of Graduate Studies / OhioLINK, 1994. http://rave.ohiolink.edu/etdc/view?acc_num=case1061219721.
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17
Camp, Robert M. "Effect of Chronic Stress Exposure on Beta-adrenergic Receptor Signaling and Fear- Learning". Kent State University / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=kent1449576849.
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18
Mehta, Ratnavali C. "Pharmacological evaluation of trimetoquinol analogs as affinity ligands for beta-adrenergic receptor systems /". The Ohio State University, 1997. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487945015617968.
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19
Potter, Paul Charles. "In Vitro studies of factors which may influence ligand binding, function, immunogenicity and genetic regulation of the Beta-2 adrenergic receptor in asthma". Doctoral thesis, University of Cape Town, 1991. http://hdl.handle.net/11427/26483.
Testo completoAbstract (sommario):
This thesis records a series of experiments conducted to gain further insight into factors which influence the expression, ligand binding and functional activity of the beta-2 adrenergic receptor. These studies were prompted by previous reports that the postulated beta-2 adrenergic receptor abnormality in allergic asthma could be induced, induced by autoantibodies. I established and optimised beta-2 adrenergic receptor ligand binding and functional assays in guinea pig lung membranes and then conducted an original study of beta adrenergic receptor expression in the guinea pig foetal lung. I found that beta adrenergic receptor expression in the foetal lung was dormant for 80% of the gestation period. After day 53 there was a surge in receptor expression which increased beyond term.
20
Yu, Esther Jeong. "Cloning and characterization of a novel β-adrenergic like receptor from Drosophila melanogaster". Thesis, University of Cambridge, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.620357.
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21
Salinas, Cristian Andres. "ROBUST EXPERIMENTAL DESIGN FOR ESTIMATING MYOCARDIAL BETA ADRENERGIC RECEPTOR CONCENTRATION USING POSITRON EMISSION TOMOGRAPHY". Case Western Reserve University School of Graduate Studies / OhioLINK, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=case1144088920.
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22
Fraundorfer, Paul F. "Functional and biochemical characterization of trimetoquinol (TMQ) analog interactions with [beta]-adrenergic receptor subtypes /". The Ohio State University, 1993. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487843314696234.
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23
Carie, Adam E. "Tumor suppressive effects of the Beta-2 adrenergic receptor and the small GTPase RhoB". [Tampa, Fla.] : University of South Florida, 2008. http://purl.fcla.edu/usf/dc/et/SFE0002330.
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24
Alsalhin, Aisha Khlani Hassan. "The role of the beta3-adrenergic receptor (β3-AR) in cardioprotection". Thesis, Stellenbosch : Stellenbosch University, 2015. http://hdl.handle.net/10019.1/97812.
Testo completoAbstract (sommario):
Thesis (MScMedSc)--Stellenbosch University, 2015.ENGLISH ABSTRACT: It is well-established that transient activation of the β-adrenergic signalling pathway with ligands such as isoproterenol, formoterol and dobutamine, elicits cardioprotection against subsequent long periods of ischaemia. Initially the focus was on the β1- and β2-adrenergic receptors (β1-AR, β2-AR), but recently the β3-AR also emerged as a potential target in the treatment of heart disease. In heart failure, β1- and β2-AR are typically known to be down-regulated while β3-ARs, on the other hand, are up-regulated (Moniotte et al., 2001). Thus, it has become important to examine the significance of the β3-AR and its downstream signalling under similar states of stress. It has been shown that β3-AR stimulation is resistant to short term agonist-promoted desensitization in vitro and in vivo (Liggett et al., 1993) and after being activated, this receptor is able to convey continual intracellular signals (Lafontan et al., 1994). Thus, it could be an ideal target for therapeutic intervention, also in ischaemic heart disease. We hypothesized that selective β3-AR stimulation during ischaemia / reperfusion may be cardioprotective, whereas selective inhibition of this receptor may prove useful in the end stages of sustained ischaemia and early reperfusion. Methods: The isolated working rat heart, subjected to 35 min of regional ischaemia (RI) and 60 min reperfusion was used as model. The β3-AR agonist (BRL37344) (1 μM) or antagonist (SR59230A) (0.1 μM) were applied as follows: (i) before 35 min RI (PT), (ii) during the last 10 min of RI (PerT) and /or (iii) at the onset of reperfusion (PostT) and (iv) administration of BRL37344 during the last 10 min of RI BRL37344 (PerT) was followed by SR59230A during first 10 min of reperfusion SR59230A (Post). The contribution of nitric oxide synthase (NOS) in β3-AR was assessed, using the non-specific NOS inhibitor, L-NAME (50 μM). Endpoints were functional recovery and infarct size. In another set of experiments BRL37344 and SR59230A were applied according to the same protocols, but the left ventricle was dissected from the heart and freeze clamped at 10 min reperfusion for Western blot analysis of extracellular signal-regulated kinase (ERK p44/p42), protein kinase B (PKB/Akt), glycogen synthase kinase-3β (GSK-3β), and endothelial nitric oxide synthase (eNOS). Data were analyzed with one or two-way analysis of variance (ANOVA). Results: Administration of the selective β3-AR agonist (BRL37344) (1μM) before 35 min RI (BRL37344 (PT), significantly reduced infarct size when compared to the non-pretreatment group (NPT) (21.43±2.52 vs 43.17±1.20, p < 0.001). BRL37344 had similar effects on infarct size when applied during the last 10 min of regional ischaemia BRL37344 (PerT) (14.94±2.34, vs NPT, p < 0.001) or at the onset of reperfusion BRL37344 (PostT) (19.06±1.81, vs NPT, p < 0.001). When BRL37344 was applied as a (PerT+PostT) strategy, infarct size was once again significantly reduced (20.55±2.01 vs 43.17±1.20, p <0.001). In contrast, administration of the β3-antagonist SR59230A according to the same protocol did not reduce infarct size and values similar to those of untreated hearts (NPT) were obtained. Surprisingly, when BRL37344 was applied during the last 10 min of regional ischaemia followed by the administration of the β3-AR antagonist (SR59230A) at the onset of reperfusion, [BRL37344 (PerT) & SR59230A (PostT)], infarct size was significantly reduced to 20.78±3.02 (p <0.001 vs NPT and SR59230A (PerT + PostT). Involvement of nitric oxide (NO) was shown since the reduction in infarct size elicited by BRL37344 was totally abolished by, L-NAME, when administered in combination with BRL37344 for 10 minutes prior to RI or at the onset of reperfusion for 10 minutes (% infarct size: 41.48±3.18 and 35.75±3.54, p <0.001 vs BRL37344 (PT) and BRL37344 (PostT), respectively. Western blot results show that PKB/Akt is activated by BRL37344 regardless of the time of administration. The intervention BRL37344 (PerT+PostT), exhibited the most significant phosphorylation of PKB/Akt (fold increase: 14.2±3.71, p<0.01 vs NPT and p<0.05 vs BRL37344 (PostT). In addition, BRL37344 (PT), (PerT), (PostT) and [BRL37344 (PerT) +SR59230A (PostT)] showed significant activation of this kinase (2.92±0.22, 5.54±0.43, 4.73±0.47, and 6.60±0.78, respectively). ERKp44/p42 however, was not significantly activated by any of the treatments. Phosphorylation of eNOS and GSK-3β was significant only in the BRL37344 (PerT+PostT) and [BRL37344 (PerT) + SR59230A (PostT)] groups. The activation of eNOS-S-1177 in the BRL37344 (PerT+PostT) group was (2.82±0.46, p<0.01 and 0.05 vs NPT and BRL37344 (PostT), respectively) and in the [BRL37344 (PerT) + SR59230A (PostT)] group was (2.26±0.48, p<0.05 vs NPT). A very significant increased phosphorylation of GSK-3β was seen in the same two groups (68.8±7.73, p<0.001 vs NPT and 25.5±5.42 vs NPT, p<0.05, respectively). Conclusion: β3-AR has potent cardioprotective effects when administered either before, during and after ischaemia during early reperfusion as indicated by the reduction in infarct size as well as activation of PKB, GSK-3β and eNOS. These beneficial effects can be linked to NO production through activation of eNOS.
AFRIKAANSE OPSOMMING: Dit is bekend dat verbygaande aktivering van die β-adrenerge seinpad, met ligande soos isoproterenol, formoterol en dobutamien, die hart teen daaropvolgende lang periodes van iskemie beskerm. Aanvanklik was die fokus op die β1- en β2-adrenerge reseptore (β1-AR, β2-AR); maar onlangs is ook die β3-AR as 'n potensiële teiken in die behandeling van hartsiektes ge-eien. In hartversaking, is dit bekend dat β1- en β2-AR afreguleer word, terwyl β3-ARs, aan die ander kant, opreguleer word (Moniotte et al., 2001). Dit het dus belangrik geword om die belang van die β3-AR en sy stroomaf seinpad onder soortgelyke strestoestande te ondersoek. Dit is bewys dat β3-AR stimulasie teen korttermyn agonis geïnduseerde desensitisering in vitro en in vivo bestand is (Liggett et al., 1993) en wanneer geaktiveer, is hierdie reseptor in staat om intrasellulêre seine voortdurend oor te dra (Granneman, 1995). Dit kan dus ‘n ideale teiken vir terapeutiese intervensie wees, ook in iskemiese hartsiekte. Ons hipotetiseer dat selektiewe β3-AR stimulasie tydens iskemie / reperfusie kardiobeskermende mag wees, terwyl selektiewe inhibisie van hierdie reseptor effektief kan wees in die eindstadia van volgehoue iskemie en vroeë herperfusie. Metodes: Die geïsoleerde werkende rothart, onderwerp aan 35 min van streeksiskemie (SI) en 60 min herperfusie, is as model gebruik. Die β3-AR agonis (BRL37344) (1μM) of antagonis (SR59230A) (0.1 μM), is as volg toegedien: (i) voor 35 min SI (PT), (ii) gedurende die laaste 10 min van SI (PerT) en / of (iii) tydens die aanvang van herperfusie (PostT) en (iv) gedurende die laaste 10 min van SI is BRL toediening BRL37344 (PerT) gevolg deur SR59230A tydens die eerste 10 min van herperfusie SR59230A (Post). Die rol van stikstofoksiedsintase (NOS) in β3-AR is met behulp van die nie-spesifieke NOS inhibitor, L-NAME (50 μM) ondersoek. Eindpunte was funksionele herstel tydens herperfusie en infarktgrootte. In 'n ander reeks eksperimente is BRL37344 en SR59230A volgens dieselfde protokolle toegedien, maar die linker ventrikel is uit die hart gedissekteer na 10 min herperfusie en gevriesklamp vir Western klad analise van ekstrasellulêre-sein gereguleerde kinase (ERK p44/p42), proteïen kinase B (PKB/Akt), glikogeen sintase kinase-3β (GSK-3β), en endoteel stikstofoksied- sintase (eNOS). Data is met een of twee-rigting variansie analise (ANOVA) ontleed. Resultate: Administrasie van die selektiewe β3-AR agonis (BRL37344) (1μM) voor 35 min SI BRL37344 (PT), het die infarktgrootte beduidend verminder vergeleke met die nie-behandelde groep (NPT) (21.43±2.52 vs 43.17±1.20, p<0.001). BRL37344 het ‘n soortgelyke effek op infarktgrootte wanneer dit gedurende die laaste 10 min van streeksiskemie BRL37344 (PerT) (14.94±2.34, vs NPT, p<0.001) of by die aanvang van herperfusie (BRL37344 (PostT) (19.06±1.81, vs NPT, p<0.001) toegedien word. Wanneer BRL37344 as 'n (PerT+PostT) strategie toegedien is, was infarktgrootte weereens beduidend verlaag (20.55±2.01 vs 43.17±1.20, p<0.001). In teenstelling hiermee, het administrasie van die β3-antagonis SR59230A volgens dieselfde protokol, nie infarktgrootte verminder nie en waardes soortgelyk aan dié van onbehandelde harte (NPT) is verkry. Interessant, wanneer BRL37344 gedurende die laaste 10 min van streeksiskemie toegedien is, gevolg deur die administrasie van die β3-AR antagonis (SR59230A) by die aanvang van herperfusie, [BRL37344(PerT) & SR59230A(PostT)], was infarktgrootte aansienlik verminder tot 20.78±3.02 (p<0.001 vs NPT en SR59230A (PerT+PostT). Die betrokkenheid van stikstofoksied (NO) is waargeneem deurdat die vermindering in infarktgrootte ontlok deur BRL37344, heeltemal deur L-NAME opgehef is, wanneer dit in kombinasie met BRL37344 vir 10 minute voor SI of by die aanvang van herperfusie vir 10 minute toegedien is (% infarktgrootte: 41.48±3.18 en 35.75±3.54, p<0.001 vs BRL37344 (PT) en BRL37344 (PostT) onderskeidelik). Western kladresultate toon dat PKB/Akt deur BRL37344 geaktiveer word ongeag die tyd van die administrasie. Die intervensie BRL37344 (PerT+PostT), toon die mees beduidende fosforilering van PKB/Akt (voudige toename: 14.2±3.71, p<0.01 vs NPT en p<0.05 vs BRL37344 (PostT). Daarbenewens het BRL37344 (PT), (PerT), (PostT) en [BRL37344 (PerT) + SR59230A (PostT)] ook beduidende aktivering van hierdie kinase tot gevolg gehad (2.92±0.22, 5.54±0.43, 4.73±0.47 en 6.60±0.78, onderskeidelik). ERKp44/p42 is egter nie deur enige van die behandelings geaktiveer nie. Fosforilering van eNOS en GSK-3β was net beduidend in die BRL37344 (PerT+PostT) en [BRL37344 (PerT) + SR59230A (PostT)] groepe. Die aktivering van eNOS-S-1177 was beduidend in die BRL37344 (PerT+PostT) en [BRL37344 (PerT) + SR59230A (PostT)] groepe. 'n Baie beduidende toename in fosforilering van GSK-3β is in dieselfde twee groepe (68.8±7.73, p<0.001 en 25.5±5.42, p<0.05 vs NPT onderskeidelik) waargeneem. Gevolgtrekking: β3-AR het kragtige kardiobeskermende effekte wanneer dit, hetsy voor, tydens en na iskemie gedurende vroeë herperfusie toegedien word, soos deur die vermindering in infarktgrootte sowel as die aktivering van PKB, GSK-3β en eNOS aangedui is. Hierdie voordelige effekte kan aan NO produksie deur aktivering van eNOS gekoppel word.
25
Crumbie, Hayley Elizabeth. "Beta-adrenergic receptor signalling and excitation-contraction coupling in the heart : impact of circadian rhythms and beta-3 receptors". Thesis, University of Leicester, 2016. http://hdl.handle.net/2381/37500.
Testo completoAbstract (sommario):
A time-of-day variation in myocardial contraction and its response to sympathetic stimulation of β-adrenoceptors (b-ADR) exists, which is reflected by time-of-day variations in intracellular calcium [Ca2+]i regulation and electrical activity. There are three isoforms of β-ADR (β1/β2/β3) and the functional outcome of each receptor differs. β1/β2-ADRs result in positive inotropism, whereas β3-ADR induces a negative inotropic effect, associated with nitric oxide (NO) signalling. The aims of this thesis were to determine the role of the β3-ADR in the time-of-day variation in the response to sympathetic stimulation previously shown by our group and to investigate the role β1-ADR, β2-ADR and β3-ADR play the control of Ca2+ regulation in isolated ventricular myocytes. Ventricular myocytes were isolated during the rest-period (ZT3) and active-period (ZT15) of male Wistar rats by enzymatic digestion. [Ca2+]i was measured in myocytes loaded with Fura-2. Arrhythmic activity was determined from video imaging, myocytes were electrically field-stimulated at 1Hz. Measurement of action potentials, transient outward (Ito) and L-type calcium (LTCC) currents were made using whole-cell patch-clamp recordings. Investigation of the time-of-day variation in response to sympathetic stimulation revealed a time-of-day variation in basal systolic [Ca2+]i and in the increase in systolic [Ca2+]i following β-ADR activation with ISO, greatest in rest-period (ZT3) myocytes. This did not appear to be governed by the time-of-day variation in action potential duration I observed or in the response of β3-ADR agonist-induced stimulation. Unlike conventional β1-ADR, β2-ADRs are tightly coupled to phosphodiesterase’s (PDE) through the inhibitory G-protein (Gi). Our data suggests this coupling to Gi and PDE activation is responsible for the reduced response of systolic Ca2+ to β2-ADR agonists, reducing the arrhythmic potential of β2-ADR activation. The reduction in systolic [Ca2+]i by β3-ADR activation with BRL37344 shows a time-of-day variation, with a greater negative inotropic response in rest-period (ZT3) myocytes, mediated via NO and PDE, leading to an increase in Sarco/Endoplasmic Reticulum Calcium ATPase (SERCA) activity but a reduction in SR Ca2+ content. This action contributes to an anti-arrhythmic action of the β3-ADR agonist BRL37344 against β1-ADR agonist induced arrhythmia. The ability of β3-ADR activation to reduce arrhythmic activity in response to further sympathetic stimulation is likely to exhibit a time-of-day variation. This work highlights the importance of chrono-pharmacology in the use of β3-ADR agonists as a treatment in arrhythmia management.
26
Skrentny, Thomas, e Brittany Traylor. "Influence of Genetic Variation of the β2 Adrenergic Receptor in Patients with Cystic Fibrosis". The University of Arizona, 2010. http://hdl.handle.net/10150/623791.
Testo completoAbstract (sommario):
Class of 2010 AbstractOBJECTIVES: Cystic fibrosis (CF) is a disease that adversely affects the lung resulting in a reduction of lung diffusion. Stimulation of the β2 adrenergic receptors results in mucocilliary clearance, and therefore, lung diffusion. We sought to determine the influence of an inhaled β-‐agonist on the diffusing capacity of the lungs for carbon monoxide (DLCO), alveolar-‐capillary membrane conductance (DM), pulmonary capillary blood volume (Vc), and peripheral oxygen saturation (SaO2) in subjects with CF and compare the data to matched healthy subjects. METHODS: To determine this we recruited 20 healthy subjects and 18 subjects with CF (age=23±7 vs. 24±4years, ht=168±8 vs. 174±12cm. wt=64±16 vs. 70±13kg, BMI= 23±4 vs. 23±3kg/m2, FEV1= 72±27 vs. 92±12%pred., VO2peak = 45±25 vs. 99±24%pred., P<0.05 for FEV1 and VO2peak, mean±SD) for the study and measured DLCO, DM, Vc and SaO2 before and 30, 60, and 90 minutes following the administration of inhaled albuterol. RESULTS: Within the healthy subjects, there were no differences in DLCO, DM, Vc, DM/Vc at baseline or in response to albuterol according to genetic variation of the ADRB2 at amino acid 27. Within the CF group, the Glu27Glu/Gln27Glu group had higher DM/Vc when compared to the Gln27Gln group at baseline. Both genotype groups had a significant decline in Vc and a significant improvement in DM/Vc and SaO2 in response to albuterol, but not in DLCO or DM. CONCLUSIONS: These results suggest that there are differences in lung diffusion and peripheral SaO2 according to genetic variants of the ADRB2 at position 27 and could play a potential role in treatment options.
27
Moore, Ann Lavinia. "Beta-adrenergic receptor antagonists and exercise radionuclide angiocardiography in patients with proven coronary artery disease". Thesis, Queen's University Belfast, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.361290.
Testo completo
28
Lundengård, Karin. "De- and Resensitisation of Cardiac β-Adrenergic Receptor Signaling : A Modelling Approach". Thesis, Linköpings universitet, Institutionen för fysik, kemi och biologi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-69076.
Testo completoAbstract (sommario):
Desensitisation is defined as a failure of a signaling pathway to respond to chronic or repeated stimulation. The β-adrenergic receptor signaling pathway of the healthy adult heart is known to desensitise, and then regain the sensitivity to stimulation if given enough time to rest between stimulations (resensitisation). The fetal heart does not desensitise, and in animal models of heart failure, a permanent desensitisation have been observed. No isolated element of the signaling pathway have yet been proven to be the sole modulator of the desensitisation behavior. Therefore a mathematical model of the signaling pathway has been constructed, minimized against theoretical desensitisation data and tested for resensitisation. The minimal models and the original model were capable of describing the theoretical de- and resensitisation of the pathway, and only one receptor type with three states was required in the minimal models, but one feedback from the kinases either to phosphorylation of the receptor or to breakdown of cAMP. The original model was also capable of describing experimental data of contraction force from chicken cardiac tissue. The cardiac tissue displays the peak behavior of the desensitisation when stimulated with ISO for ten minutes, and resensitises in less than 5 minutes.
29
Adejare, Adeboye. "Part I. fluorinated benzylimidazolines as agents for probing the [alpha]-adrenergic receptor. part II. synthesis, [beta]-adrenergic and antiplatelet activities of trimetoquinol analogs /". The Ohio State University, 1985. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487260135356326.
Testo completo
30
Hammon, Harald. "Distribution and density of alpha- and beta-adrenergic receptor : binding sites in the bovine mammary gland /". [S.l.] : [s.n.], 1993. http://www.stub.unibe.ch/html/haupt/datenbanken/diss/bestell.html.
Testo completo
31
Kwok, Wing-yee Winnie, e 郭穎怡. "Polymorphisms of the {221}2-adrenergic receptor gene associated with asthma among Chinese in Hong Kong". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2003. http://hub.hku.hk/bib/B29247330.
Testo completo
32
LaBranche, Timothy Paul. "Characterization of the Beta-2 Adrenergic Receptor Mechanism in Bovine Neutrophils, and Some Effects of Inflammatory Stimuli on its Function". Diss., Virginia Tech, 2005. http://hdl.handle.net/10919/27275.
Testo completoAbstract (sommario):
The bovine polymorphonuclear leukocyte (neutrophil) is a central component of the acute inflammatory response, and is capable of reacting to a myriad of pro-inflammatory chemical signals that have been characterized in the context of bovine respiratory disease (BRD). Human neutrophils and bovine macrophages are known to react to pro-inflammatory signals as well; however, they are also capable of responding to anti-inflammatory signals from the autonomic nervous system. In particular, activation of the beta2-adrenergic receptor on these cells decreases several aspects of inflammatory activity, including reactive oxygen species production, chemotaxis, degranulation, and inflammatory mediator production. Dysfunction of beta-adrenergic receptors is known to contribute to the pathophysiology of numerous diseases in both people and animals. For example, congestive heart failure, asthma, cystic fibrosis, atopic dermatitis, pheochromocytoma, myasthenia gravis, hypertension, and sepsis have all been linked to decreased beta1- / beta2-adrenergic receptor density (depending on the cell type) and / or uncoupling of the respective receptor from its effector enzyme, adenylyl cyclase. Dysfunction of the beta2-adrenergic receptor mechanism has also been described in pulmonary airway and vascular smooth muscle tissue from cattle, sheep, and rats exposed to Manheimia haemolytica, which provides insight into the pathophysiology of BRD. Despite the prominent role of the bovine neutrophil in the acute inflammatory stage of BRD, and despite the potential for dysfunction following excessive exposure to inflammatory stimuli, there are no reports that describe the presence of the beta2-adrenergic receptor on bovine neutrophils, nor function of the components responsible for its signal transduction cascade. Without complimentary work with bovine neutrophils, using data from human neutrophils to examine treatment options for the acute inflammatory stage of BRD is unrealistic. For this reason, the present dissertation proposed that 1) bovine neutrophils possess the beta2-adrenergic receptor mechanism, 2) components of the beta2-adrenergic receptor mechanism work in concert to increase bovine neutrophil adenosine 3,5-cyclic monophosphate (cAMP) levels and suppress superoxide anion production, and 3) the beta2-adrenergic receptor mechanism is dysfunctional following exposure to inflammatory stimuli. Using the nonselective beta1- / beta2-adrenergic receptor antagonist [3H]CGP-12177 we observed a maximum specific binding density (Bmax) value of 0.19 fmol per 100,000 bovine neutrophils. Although this value is approximately equal to what we observed with dairy cow neutrophils, human neutrophil Bmax values with this radioligand are anywhere from five to ten-fold greater, which suggests a significant species difference. We further defined the adrenergic receptor population on bovine neutrophils to be dominated by the beta2-subtype. Next, we characterized the function of beta2-adrenergic receptors by stimulating cAMP production with the beta2-adrenergic receptor agonist, terbutaline. The role of the beta2-subtype was confirmed when the terbutaline-mediated effect was negated by ICI-118,551, a beta2-adrenergic receptor antagonist. Also, the role of the phosphodiesterase enzyme in cAMP recycling in bovine neutrophils was illustrated, as the terbutaline-mediated rise in cAMP concentration was dependent upon phosphodiesterase inhibition by 3-isobutyl-1-methylxanthine (IBMX). This study confirms the anti-inflammatory nature of the beta2-adrenergic receptor on bovine neutrophils by demonstrating the ability of terbutaline and IBMX to decrease superoxide anion production in a dose-dependent manner. The synthetic cAMP analog, 8-bromo-cAMP also decreased superoxide anion production, but the effect was time-dependent because of its need to diffuse across the cell membrane. Moreover, IBMX exaggerated the terbutaline-mediated effect on superoxide anion production, while cAMP exaggerated the IBMX-mediated effect on superoxide anion, demonstrating that the beta2-adrenergic receptor acts in concert with adenylyl cyclase, while the phosphodiesterase enzyme functions to decrease their signal. By increasing the dose of the inflammatory stimulant opsonized zymosan eight-fold, we were able to eliminate the ability of various concentrations of terbutaline and IBMX to reduce superoxide anion production. We sought to provide a more specific demonstration of this phenomenon by activating protein kinase C (PKC) via phorbol 12-myristate 13-acetate (PMA) administration. However, preincubation with PMA actually increased terbutaline-mediated cAMP production, in a dose and time-dependent manner. At this time, we cannot explain why increasing the dose of opsonized zymosan and PMA had opposite effects on beta2-adrenergic receptor mechanism function. The answer may reside in the many reported functions of PKC isoforms. Additional studies that identify the PKC isoform repertoire in bovine neutrophils may illustrate the potential for selective inhibition, and may lead to more specific identification and treatment of beta2-adrenergic receptor mechanism dysfunction. Also, it remains to be seen how the various components of the bovine neutrophil beta2-adrenergic receptor mechanism function in-vivo during the acute inflammatory stage of BRD.Ph. D.
33
Griffith, D. N. W. "The cerebral circulation in diabetes mellitus and hypertension and its responses to beta adrenergic receptor-blocking drugs". Thesis, University of Cambridge, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.599714.
Testo completo
34
Herko, Kara, Benjamin Guthrie e Eric Snyder. "Genetic Variation of the BETA-2 Adrenergic Receptor and the Bronchodilatory Response to Albuterol in Patients with Cystic Fibrosis". The University of Arizona, 2012. http://hdl.handle.net/10150/614494.
Testo completoAbstract (sommario):
Class of 2012 AbstractSpecific Aims: We sought to determine the influence of genetic variation of ADRB2 on the airway response to albuterol in patients with CF when compared to matched healthy controls at baseline and at 60 minutes following the administration of albuterol (2.5mg diluted in 3ml normal saline). Methods: Baseline pulmonary function (forced vital capacity, FVC, forced expiratory flow in 1-second, FEV1, mid-maximal expiratory flow, MMF, and forced expiratory flow at 50% of the FVC) was assessed in 17 patients with CF and 31 healthy subjects. Main Results: As expected, the healthy group had higher baseline pulmonary function when compared to the CF group (FVC=97±3 vs. 83±5; FEV1=95±3 vs. 72±6; MMF=90±4 vs. 54±8, % predicted for healthy and CF, respectively, mean±SE, p<0.05 for all. We compared Arg16Arg to Arg16Gly/Gly16Gly subjects. There was no effect of genotype on the response to albuterol in healthy subjects. However, in the CF group, we found that the Arg16Arg group (n=6) had an attenuated response to β-agonist when compared to the Gly-containing group (n=11) (FVC=0±0.9 vs. 6±3: FEV1=3±1 vs. 7±4: MMF=12±3 vs. 12±5 % change, for Arg16Arg and Gly-containing groups, respectively, p<0.05 for FVC, p=0.06 for FEV1). Conclusions: These results demonstrate a differential response to β-agonists according to genetic variation of the ADRB2 at amino acid 16. Due to the differences in FVC and FEV1 but not in MMF, these data suggest that the genetic difference in airway function is primarily in bronchodilation of the larger airways.
35
Calderón, Diego Mauricio Bravo. "Migração e invasão do câncer de boca via ativação de receptor beta 2 adrenérgico por mediador do estresse". Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/25/25150/tde-10032016-163155/.
Testo completoAbstract (sommario):
A ativação do receptor beta 2 adrenérgico (β2-AR), pelos mediadores químicos do estresse, pode induzir efeitos estimuladores ou inibidores na migração e invasão celular, dependendo do tipo de tumor maligno. A importância deste receptor na evolução do câncer de boca não está totalmente esclarecida. O objetivo deste estudo foi verificar a expressão do β2-AR em linhagens de carcinomas espinocelular de boca (SCC-9 e SCC-25), e investigar o papel da ativação deste receptor pela norepinefrina e de seu bloqueio por um antagonista na migração e invasão destas células neoplásicas. As células SCC-9 e SCC-25 foram investigadas quanto à expressão gênica e proteica do β2-AR, respectivamente, pelo RT-qPCR e pelo Western blot. A migração e a invasão celular foram analisadas pelo ensaio de cicatrização de feridas e pelo sistema de câmeras de invasão Transwell, respectivamente. Diferentes concentrações (0,1; 1 e 10μM) de norepinefrina foram utilizadas para estimular e 1μM de propranolol foi empregado para bloquear os receptores beta adrenérgicos nas células neoplásicas. As diferenças das médias obtidas nos experimentos de invasão e migração de SCC-9 e SCC-25 e da expressão proteica do β2-AR, foram comparadas pelo teste t de Student com nível de significância de 5%. Os resultados mostraram que a expressão gênica e proteica do β2-AR foi verificada em ambas as linhagens de câncer de boca. A concentração de 10μM de norepinefrina inibiu, significativamente (p≤0,05), a migração e invasão celular de SCC-9 e SCC-25, sendo este efeito mais acentuado nas células SCC-25. Além disso, houve uma redução significativa (p≤0,05) do efeito da norepinefrina na migração celular quando os β2-AR foram inibidos pelo propranolol. Adicionalmente, o bloqueio dos β-ARs pelo propranolol reverteu parcialmente o efeito da norepinefrina na capacidade invasiva de SCC-9 e SCC-25. Estes resultados comprovam que a norepinefrina, via ativação do β2-AR, reduziu a migração e a invasão das células do carcinoma espinocelular de boca e, portanto, o uso de agonistas dos receptores beta-adrenérgicos poderia se tornar um alvo terapêutico adjuvante no tratamento desta neoplasia maligna.The activation of beta 2 adrenergic receptor (β2-AR), by chemical mediators of stress, can induce stimulatory or inhibitory effects on cell migration and invasion, depending on the type of malignancy. The importance of this receptor in the oral cancer outcome is not fully understood. The aim of this study was to verify β2- AR expression in oral squamous cell carcinoma cell lines (SCC-9 and SCC-25), and to investigate the role of activation of this receptor by norepinephrine and its blockade by an antagonist in migration and invasion of these neoplastic cells. SCC-9 and SCC-25 cells were investigated for gene and protein expression of β2-AR, respectively, by RT-qPCR and Western blot. The cell migration and invasion were analyzed by wound healing assay and Transwell invasion camera system, respectively. Different concentrations (0.1, 1 and 10μM) of norepinephrine were used to stimulate and 1μM propranolol was used to block the beta adrenergic receptors on cancer cells. Differences in mean values of the invasion and migration assays of SCC-9 and SCC-25 and β2-AR protein expression were compared by the Student t test with 5% significance level. The results showed that β2-AR gene and protein expression was verified in both oral cancer cell lines. The concentration of 10μM of norepinephrine inhibited significantly (p≤0.05), cell migration and invasion of SCC-9 and SCC-25, being the most pronounced effect in SCC-25 cells. Furthermore, there was a significant reduction (p≤0.05) of norepinephrine effect on cell migration when the β2-AR was inhibited by propranolol. In addition, blockade of β-ARs by propranolol partially reversed the effect of norepinephrine on the invasiveness of SCC-9 and SCC-25. These results show that norepinephrine via β2-AR activation, reduced the migration and invasion of oral squamous cell carcinoma cells and, therefore, the use of beta-adrenergic receptors agonists could become an adjuvant therapeutic target in the treatment of this malignancy.
36
Calderón, Diego Mauricio Bravo. "Expressão de receptor beta-2 adrenérgico em carcinoma espinocelular de boca e sua associação com a evolução clínica tumoral". Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/25/25150/tde-27072011-095304/.
Testo completoAbstract (sommario):
Os hormônios produzidos durante o estresse e seus receptores específicos têm sido amplamente envolvidos com a progressão do câncer. O objetivo deste estudo foi avaliar a expressão dos receptores β2 adrenérgicos pelas células malignas de carcinomas espinocelulares de boca (CEC) e sua correlação com as a características clínicas, evolução e o prognóstico dos pacientes. Um total de 106 pacientes portadores de CEC de boca em estádios clínicos II, III e IV, tratados no Departamento de Cirurgia de Cabeça e Pescoço e Otorrinolaringologia do Hospital de Câncer A.C. Camargo, São Paulo, Brasil, no período de 1970 a 2000, foram analisados quanto aos dados demográficos, história clínica, localização e extensão do tumor, classificação pelo sistema TNM-UICC, tratamento e evolução tumoral. Analisaram-se também as características histopatológicas, índice de malignidade tumoral e a expressão imuno-histoquímica do receptor β2 adrenérgico pelas células malignas no front de invasão tumoral. A associação da expressão do receptor β2 adrenérgico e as variáveis clínicas ou microscópicas foi calculada pelo teste do qui quadrado ou teste exato de Fisher. As probabilidades de sobrevida global e específica por câncer em 5 e 10 anos foram calculadas pelo estimador produto-limite de Kaplan-Meier, comparadas pelo test de long-rank e pelo modelo de regressão múltiplo de Cox. A expressão do receptor β2 adrenérgico foi detectada na membrana e no citoplasma das células malignas da maioria dos CECs de boca (72,6%) e, significativamente associada ao etilismo (p=0,021), tabagismo e etilismo simultâneo (p=0,014) e estadiamento T (p=0,07). Os pacientes cujos tumores demonstraram expressão positiva do receptor β2 adrenérgico apresentaram maiores taxas de sobrevida global (p=0,001) e específica por câncer (p=0,004), quando comparadas aquelas dos pacientes com tumores com ausência da expressão desta proteína. Esses resultados sugerem que a expressão do receptor β2 adrenérgico nas células malignas da região do front de invasão tumoral constitui um fator prognóstico favorável em pacientes com carcinoma espinocelular de boca e pode ser utilizada como alvo de novas estratégias farmacológicas antineoplásicas.The stress related hormones and their specific receptors have been widely involved with cancer progression. The aim of this study was to evaluate the expression of β2 adrenergic receptor by malignant cells in oral squamous cell carcinoma (OSCC) and its correlation with clinical characteristics, outcome and patients prognosis. A total of 106 patients with OSCC in clinical stages II, III and IV submitted to surgical treatment at the Head and Neck Surgery and Otorhinolaryngology Department, of the Cancer Hospital A.C. Camargo, São Paulo, Brazil, from 1970 to 2000, were analyzed for demographics data, clinical history, location, tumor extension, stage by the TNM-UICC, treatment and tumor outcome. In addition, we investigated the morphologic features, the histopathological malignant index and the immunohistochemical expression of β2 adrenergic receptor by malignant cells of the invasive front of tumor. Chi-square test or Fishers exact test was used to analyze the association among β2 adrenergic receptor expression and the clinical or morphologic variables. The probability of overall and cancer specific survival in 5 and 10 years were calculated by Kaplan-Meier method and the prognostic value of the clinical and morphologic variables was obtained by Cox regression model. Most of OSCCs (72,6%) showed the β2 adrenergic receptor expression in cytoplasm and cell membrane of malignant cells. In OSCC, positive β2 adrenergic receptor expression was significantly associated with alcoholism (p=0.021), simultaneous consumption of alcohol and tobacco (p=0.014) and T stage (p=0.07). OSCC patients with positive expression of β2 adrenergic receptor showed higher rates of overall survival (p=0.001) and cancer specific (p=0.004) than those patients with tumors without expression of this protein. These results suggest that the β2 adrenergic receptor expression by malignant cells in the invasive front of tumor is a favorable prognostic factor in patients with OSCC and can be used as a target for new anti-neoplastic pharmacological strategies.
37
Herko, Kara, e Benjamin Guthrie. "Genetic Variation of the BETA-2 Adrenergic Receptor and the Bronchodilatory Response to Albuterol in Patients with Cystic Fibrosis". The University of Arizona, 2012. http://hdl.handle.net/10150/623639.
Testo completoAbstract (sommario):
Class of 2012 AbstractSpecific Aims: We sought to determine the influence of genetic variation of ADRB2 on the airway response to albuterol in patients with CF when compared to matched healthy controls at baseline and at 60 minutes following the administration of albuterol (2.5mg diluted in 3ml normal saline). Methods: Baseline pulmonary function (forced vital capacity, FVC, forced expiratory flow in 1-second, FEV1, mid-maximal expiratory flow, MMF, and forced expiratory flow at 50% of the FVC) was assessed in 17 patients with CF and 31 healthy subjects. Main Results: As expected, the healthy group had higher baseline pulmonary function when compared to the CF group (FVC=97±3 vs. 83±5; FEV1=95±3 vs. 72±6; MMF=90±4 vs. 54±8, % predicted for healthy and CF, respectively, mean±SE, p<0.05 for all. We compared Arg16Arg to Arg16Gly/Gly16Gly subjects. There was no effect of genotype on the response to albuterol in healthy subjects. However, in the CF group, we found that the Arg16Arg group (n=6) had an attenuated response to β-agonist when compared to the Gly-containing group (n=11) (FVC=0±0.9 vs. 6±3: FEV1=3±1 vs. 7±4: MMF=12±3 vs. 12±5 % change, for Arg16Arg and Gly-containing groups, respectively, p<0.05 for FVC, p=0.06 for FEV1). Conclusions: These results demonstrate a differential response to β-agonists according to genetic variation of the ADRB2 at amino acid 16. Due to the differences in FVC and FEV1 but not in MMF, these data suggest that the genetic difference in airway function is primarily in bronchodilation of the larger airways.
38
Visser, Thomas Jakob. "Development of new muscarinic and [beta]-adrenergic receptor radiopharmaceuticals for Positron Emission Tomography application to lungs, heart and brain /". [S.l. : [Groningen : s.n.] ; University Library Groningen] [Host], 1997. http://irs.ub.rug.nl/ppn/297496689.
Testo completo
39
Houle, Melanie Taghon. "Enhanced in vivo and in vitro response to Beta-2 Adrenergic Receptor Stimulation in animals susceptible to Ventricular Fibrillation /". The Ohio State University, 2000. http://rave.ohiolink.edu/etdc/view?acc_num=osu1488192960167032.
Testo completo
40
Imura, Tetsuya. "Differential expression of small heat shock proteins in reactive astrocytes after focal ischemia : possible role of beta adrenergic receptor". Kyoto University, 2000. http://hdl.handle.net/2433/180858.
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Gonçalves, Andrezza Neves. "Investigação do mecanismo bioquímico in vitro da interação da metaloprotease da matriz 2 (MMP-2) com o receptor beta 1 adrenérgico". Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/17/17131/tde-01022019-102035/.
Testo completoAbstract (sommario):
As metaloproteases da matriz (MMPs) são enzimas proteolíticas que participam da degradação da matriz extracelular no organismo de vertebrados. Estudos mostram a grande importância dessas enzimas no processo de remodelação do tecido cardíaco, além de sugerirem a participação da MMP-2 em doenças cardiovasculares. Em estudo recente foi demonstrado que as MMPs clivam o receptor ?2-adrenérgico, contribuindo para o aumento do tônus arteriolar de ratos espontaneamente hipertensos (SHR). Acredita-se que processo semelhante possa ser verificado em relação ao receptor ?-1 adrenérgico e proteínas das junções, que são fundamentais para o funcionamento do coração. As análises in sílico realizadas mostraram regiões prováveis de clivagem pela metaloprotease da matriz 2 humana recombinante (rhMMP-2) na porção extracelular, especificamente na região Nterminal deste receptor, no entanto, as análises de comparação de similaridade de substratos não apresentaram resultados significativos, embora os resultados preliminares obtidos no teste in vitro mostraram que houve hidrolise logo no início do peptídeo sintético ASPPASLLPPAS, entre os resíduos alanina e serina, entre as duas prolinas e por fim entre o resíduo de prolina e alanina, regiões com grandes chances de ocorrer a hidrólise, pois o substrato nativo desta enzima é o colágeno que é composto por uma cadeia polipeptídica com uma sequência de repetições onde geralmente temos glicina-X-Y, onde X normalmente é uma prolina e Y frequentemente uma hidroxiprolina, e raramente lisina e hidroxilisina, no entanto a replicação deste experimento não apresentou o mesmo resultado. Já os resultados obtidos no western blotting mostraram que a expressão do receptor é diminuída quando os cardiomiócitos são previamente tratados com 40mM e 120mM de rhMMP- 2 e esse efeito tem uma reversão significativa quando as células são previamente tratadas com inibidores doxiciclina ou ONO-4817, corroborando com os trabalhos apresentados na literatura em que a rhMMP-2 atua no receptor ?1adrenérgico.Matrix metalloproteinases (MMPs) are proteolytic enzymes that participate in the degradation of the extracellular matrix in the vertebrate organism. Studies show the great importance of these enzymes in the remodeling process of cardiac tissue, besides suggesting the participation of MMP-2 in cardiovascular diseases. In a recent study, MMPs were shown to cleave the ?2-adrenergic receptor, contributing to the increase in arteriolar tone of spontaneously hypertensive rats (SHR). It is believed that a similar process can be verified also in the ?-1 adrenergic receptor and junction proteins, which are fundamental to the heart function. The in situ analyzes performed revealed sections prone to be cleaved by matrix metalloproteinase 2 recombinant human (rhMMP-2) in the extracellular portion, specifically in the Nterminal region of this receptor, however, the comparative analyzes of the similarity of substrates did not present significant results, but those obtained in the in vitro test showed that there was hydrolysis right at the beginning of the synthetic peptide ASPPASLLPPAS, between alanine and serine residues, between the two proline and finally between the proline residue and alanine. Hydrolysis among proline residues was expected, even though it was not predicted for in silica cleavage, since the native substrate of this enzyme is collagen, which is composed of a polypeptide chain with a sequence of repetitions in which it usually has glycine-XY, where X usually is a proline and Y often a hydroxyproline, and rarely lysine and hydroxylysine, however the replication of this experiment di not present the same result. The obtained results in western blotting have presented that receptor expression is decreased when cardiomyocytes are pretreated with 40mM and 120mM rhMMP-2 and this effect has a significant reversion when cells are pretreated with doxycycline or ONO-4817 inhibitors, supporting previous studies which demonstrate that rhMMP- 2 acts on the ? 1 adrenergic receptor.
42
Chen, Xiaochuan, Amy C. Kelly, Dustin T. Yates, Antoni R. Macko, Ronald M. Lynch e Sean W. Limesand. "Islet adaptations in fetal sheep persist following chronic exposure to high norepinephrine". BIOSCIENTIFICA LTD, 2017. http://hdl.handle.net/10150/623222.
Testo completoAbstract (sommario):
Complications in pregnancy elevate fetal norepinephrine (NE) concentrations. Previous studies in NE-infused sheep fetuses revealed that sustained exposure to high NE resulted in lower expression of α2-adrenergic receptors in islets and increased insulin secretion responsiveness after acutely terminating the NE infusion. In this study, we determined if the compensatory increase in insulin secretion after chronic elevation of NE is independent of hyperglycemia in sheep fetuses and whether it is persistent in conjunction with islet desensitization to NE. After an initial assessment of glucose-stimulated insulin secretion (GSIS) at 129 ± 1 days of gestation, fetuses were continuously infused for seven days with NE and maintained at euglycemia with a maternal insulin infusion. Fetal GSIS studies were performed again on days 8 and 12. Adrenergic sensitivity was determined in pancreatic islets collected at day 12. NE infusion increased (P < 0.01) fetal plasma NE concentrations and lowered (P < 0.01) basal insulin concentrations compared to vehicle-infused controls. GSIS was 1.8-fold greater (P < 0.05) in NE-infused fetuses compared to controls at both one and five days after discontinuing the infusion. Glucose-potentiated arginine-induced insulin secretion was also enhanced (P < 0.01) in NE-infused fetuses. Maximum GSIS in islets isolated from NE-infused fetuses was 1.6-fold greater (P < 0.05) than controls, but islet insulin content and intracellular calcium signaling were not different between treatments. The half-maximal inhibitory concentration for NE was 2.6-fold greater (P < 0.05) in NE-infused islets compared to controls. These findings show that chronic NE exposure and not hyperglycemia produce persistent adaptations in pancreatic islets that augment β-cell responsiveness in part through decreased adrenergic sensitivity.
43
Kam, Wan-lung Kenneth. "Effect of ovariectomy and estrogen replacement on the [beta]-Adrenergic receptor signaling pathway and intracellular Ca2+ homeostasis in the rat heart". Click to view the E-thesis via HKUTO, 2005. http://sunzi.lib.hku.hk/hkuto/record/B31473143.
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44
Parsa-Nezhad, Maryam. "Ex vivo evaluation of reduced myocardial beta-adrenergic receptor binding in the streptozotocin-treated hyperglycaemic rats using (S)-[(3)H]CGP12177". Thesis, University of Ottawa (Canada), 2008. http://hdl.handle.net/10393/28013.
Testo completoAbstract (sommario):
Type II Diabetes Mellitus (DM) is a common metabolic disorder that affects millions of people worldwide. Elevated blood glucose levels in type II DM is associated with altered sympathetic nervous system (SNS) activity and enhanced noradrenaline (NA). Persistent NA release, in turn, leads to alterations in beta-adrenergic receptor (betaAR) density and downstream signalling. A common complication of diabetes is cardiovascular disease. In this project, myocardial betaAR density was evaluated in hyperglycaemic streptozotocin (STZ)-treated rats fed high fat diet (HFD), using betaAR antagonist (S)-[3H]CGP12177. At 30 minutes post injection, the radiotracer exhibited specific binding in myocardial regions, brown adipose tissue and kidney, and was capable of measuring reduced binding to betaARs. A subset of HFD moderate-STZ treated rats became hyperglycaemia, whereas the remainder maintained euglycaemia. At 10 days post-STZ, no alteration was observed in tracer binding in either sub-group. At 56 days, hyperglycaemic rats displayed a significant reduction in specific binding to betaARs in myocardial regions (30-40%), while no alteration was observed in euglycaemics or controls. This finding suggests a strong association between sustained hyperglycaemia and alterations in SNS activity and PAR binding.
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Padro, Caroline Jeannette. "A Study of the Distal Molecular Mechanism by which Beta-2 Adrenergic Receptor Stimulation on a B Cell Regulates IgE Production". The Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1384763500.
Testo completo
46
Enoshiri, Tatsuki. "Beta adrenergic receptor blockers reduce the occurrence of keloids and hypertrophic scars after cardiac device implantation: a single-institution case-control study". Kyoto University, 2017. http://hdl.handle.net/2433/227549.
Testo completo
47
Muumba, Justice. "Association of Single Nucleotide Polymorphisms in the Beta-2- Adrenergic Receptor Gene with Growth, Carcass and Meat Characteristics in Beef Steers and Heifers". Thesis, The University of Arizona, 2007. http://hdl.handle.net/10150/193363.
Testo completoAbstract (sommario):
A total of 693 beef steers and heifers of six breeds were utilized in an association study. Traits analyzed were birth weight (BW), weaning age (WA), adjusted weaning weight (WW), hot carcass weight (HCW), marbling score (MS), 12th rib fat thickness (FT), Longissimus dorsi muscle area (LM), estimated kidney, pelvic and heart fat (KPH); and yield grade (YG). Five single nucleotide polymorphisms (SNPs) in the beta-2 adrenergic receptor (ADRB2) gene were evaluated as markers for beef traits. One SNP was uninformative and was discarded. There was an interaction of gender by A11C SNP on WA (P<0.05), WW (P=0.1) and KPH (P=0.05). An interaction was detected between the C1027T SNP and gender on WA (P<0.05) and WW (P<0.1). There was no association (P>0.1) between A11C, C41T and C1027T SNP's with the remaining traits. These results suggest that SNP's for ADRB2 gene might be useful for WA, WW and KPH traits.
48
Majid, Samia. "Synthèse, marquage à l'iode et comportement biologique de [beta]-bloquants potentiels". Université Joseph Fourier (Grenoble), 1994. http://www.theses.fr/1994GRE10074.
Testo completoAbstract (sommario):
Parmi les differents recepteurs myocardiques, les plus interessants d'un point de vue physiopathologique, sont les recepteurs beta adrenergiques. La synthese de beta-bloquants emetteurs gamma (#1#2#3i) utilisables in vivo dans le denombrement de ces recepteurs, a ete l'objectif essentiel de ce travail. Ce projet nous a conduits a la synthese d'analogues iodes de beta-bloquants connus: analogues du cgp12177 dans lequel le groupement tertiobutyle a ete remplace par le groupement homoveratryle, l'iodation de ce compose l'a rendu trop lipophile. Analogues du h87/07, avec une chaine en position 4 comportant le motif beta-iodoethoxy (stabilisation de la liaison c-i). Un de ces composes est un antagoniste pur, malheureusement trop lipophile pour etre utilise in vivo. Analogues du practolol, dans lequel le motif acetylamino en position 4 est remplace par nhco(ch#2)#nch=chi (n=2,0). Les meilleurs resultats biologiques ont ete obtenus avec n=2. Ce compose appele ami-9, est le premier radioligand iode marqueur des recepteurs beta-adrenergiques permettant d'envisager l'etude de ces derniers in vivo
49
Martinez, Marina G. "Genetic Variation of the Beta-2 Adrenergic Receptor and the Phenylethanolamine N-Methyltransferase Enzyme: Influence on Catecholamines, Cardiovascular Regulation, and the Cardiopulmonary Response to Albuterol". Diss., The University of Arizona, 2014. http://hdl.handle.net/10150/317802.
Testo completoAbstract (sommario):
Hypertension, or chronic blood pressure elevation, affects approximately a third of American adults and is responsible for $70 billion dollars annually in medical costs. Recent studies have attempted to identify genetic variants that influence cardiopulmonary function, including blood pressure regulation. This study seeks to determine whether a polymorphism in position -182 of the gene encoding the phenylethanolamine N-methyltransferase (PNMT) enzyme, which converts norepinephrine to epinephrine, influences catecholamine levels and cardiovascular function. Secondly, this study seeks to explore whether a polymorphism at amino acid position 16 of the beta-2 adrenergic receptor (B2AR) affects the cardiovascular response to albuterol in healthy individuals; this study also explores the pulmonary response to albuterol in healthy subjects and patients with cystic fibrosis according to B2AR genotype. All subjects were genotyped and stratified according to genotype. Baseline measurements were taken. Albuterol was administered via nebulizer. Cardiopulmonary measurements were taken again at 30-, 60-, and 90- minutes post-albuterol administration. This study found that the PNMT polymorphism at position -182 influences circulating epinephrine, the epinephrine:norepinephrine ratio, and cardiac output. The B2AR polymorphism at amino acid position 16 affects the percent change in systemic vascular resistance in response to albuterol administration in healthy subjects. Furthermore, this study found that the B2AR polymorphism at amino acid 16 affects the change in forced vital capacity following albuterol administration in cystic fibrosis subjects.
50
Santos, Larissa Ferreira dos. "Controle neurovascular do fluxo sanguíneo muscular e da atividade nervosa simpática durante o exercício em pacientes após síndrome isquêmica miocárdica instável com polimorfismos do receptor \'beta\'2-adrenérgico Gln27Glu". Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/39/39132/tde-07042015-144133/.
Testo completoAbstract (sommario):
A síndrome isquêmica miocárdica instável (SIMI) leva a importantes alterações neurovasculares, tais como à hiperativação simpática e a diminuição do fluxo sanguíneo muscular (FSM) tanto em repouso como durante manobras fisiológicas como o exercício. A presença de alguns polimorfismos na genética humana, como o dos receptores \'beta\'2-adrenérgicos Gln27Glu, apresenta importante associação com a funcionalidade cardiovascular em indivíduos saudáveis. Contudo, não é conhecido se em pacientes com SIMI, a presença dos polimorfismos do receptor \'beta\'2-adrenérgico leva a respostas neurovasculares distintas durante o exercício, e, ainda, se o treinamento físico poderá modificar essa resposta. OBJETIVOS: Estudar a influência do polimorfismo do receptor \'beta\'2-adrenérgico Gln27Glu no controle neurovascular da atividade nervosa simpática muscular (ANSM) e do FSM em repouso e durante o exercício físico de preensão de mão, em pacientes com SIMI e, num segundo momento, avaliar o efeito do treinamento físico nas respostas neurovasculares durante o exercício nestes pacientes. MÉTODOS: Inicialmente, foram selecionados para o estudo, 78 pacientes com SIMI com fração de ejeção >= 45%, no momento da hospitalização. Um mês após o evento isquêmico, 61 pacientes retornaram para as avaliações iniciais. Os pacientes foram genotipados e posteriormente divididos em dois grupos de acordo com o polimorfismo Gln27Glu do receptor \'beta\'2-adrenérgico: 1- Gln27Gln (CC, n=35) e 2- Gln27Glu+Glu27Glu (CG+GG, n=26). Destes, 29 pacientes concordaram em participar de um protocolo de treinamento físico por um período de 8 semanas, sendo que, 25 finalizaram o protocolo (CC, n=17; CG+GG, n=8). A avaliação do controle neurovascular foi realizada em repouso e durante o exercício físico de preensão de mãos em 30% da contração voluntária máxima. Foram avaliados a ANSM, medida pela técnica direta de microneurografia, o FSM, medido pelo método de pletismografia de oclusão venosa, a pressão arterial, medida pelo método oscilométrico indireto e a frequência cardíaca, pelo eletrocardiograma. Todas as avaliações foram realizadas nos pacientes um mês após o evento isquêmico e, para aqueles que participaram do protocolo de treinamento físico, foram repetidas após 8 semanas de intervenção. RESULTADOS: Um mês após o evento isquêmico, a ANSM (P=0,26) e a pressão arterial média (PAM, P=0,14) de repouso foram semelhantes entre os grupos com genótipo CC e CG+GG. Entretanto, durante o exercício, a resposta da ANSM foi maior no grupo CC quando comparado com o grupo com CG+GG (\'delta\'=11±2 vs. 4±2 disparos/100batimentos, P=0,02). Adicionalmente, a resposta de PAM foi maior no grupo CC quando comparado ao grupo CG+GG (\'delta\'=24±2 vs. 18±2 mmHg, P=0,04). A resposta de condutância vascular no antebraço (CVA) durante o exercício foi semelhante entre ambos os grupos. Após treinamento físico a ANSM basal diminuiu no grupo com genótipo CC (63±3 vs. 48±5 disparos/100batimentos, P <0,001), mas não no grupo com genótipo CG+GG (70±4 vs. 55±5 disparos/100batimentos, P =0,06). De forma semelhante, durante o exercício, o treinamento físico diminuiu o nível (P= 0,007) e a resposta da ANSM (\'delta\'=12±2 vs. 5±2 disparos/100batimentos, P=0,02) no grupo com genótipo CC, mas não no grupo com genótipo CG+GG (P=0,10) e (\'delta\'=7±3 vs. 7±3 disparos/100batimentos, P=0,96), respectivamente. O treinamento físico não modificou os níveis de PAM e CVA, durante o exercício, em ambos os grupos. Contudo, analisando-se o período pós-treinamento físico, o grupo CG+GG apresentou resposta de PAM menor (P=0,01) e CVA maior (P=0,03) durante o exercício quando comparado ao grupo CC. CONCLUSÃO: Pacientes com SIMI, portadores do genótipo CC do receptor \'beta\'-adrenérgico apresentam resposta aumentada da ANSM durante a manobra fisiológica de exercício, quando comparados aos pacientes com genótipo CG+GG. O treinamento físico reverte esta resposta exacerbada de ANSM nos pacientes com genótipo CC. Esses resultados sugerem um risco cardiovascular aumentado nos pacientes com SIMI com genótipo CC do receptor \'beta\'-adrenérgico. Por outro lado, o treinamento físico deve ser fortemente recomendado para esses pacientes, sobretudo naqueles com o genótipo CC.Acute coronary syndrome (ACS) leads to important neurovascular abnormalities such as sympathetic hyperactivity and decreased forearm blood flow (FBF) at rest and during physiological maneuvers as exercise. The presence of some polymorphisms in human genetics, as the β2-adrenoceptor Gln27Glu, presents a significant association with cardiovascular functionality in healthy subjects. However, it is not known whether in patients with ACS, the presence of polymorphisms of the β2-adrenoceptor leads to distinct neurovascular responses during exercise, and if the exercise training can modify this response. OBJECTIVES: To study the influence of Gln27Glu \'beta\'2-adrenoceptor polymorphisms on neurovascular control of muscle sympathetic nerve activity (MSNA) and FBF at rest and during handgrip exercise, in patients with ACS; and to evaluate the effect of exercise training on neurovascular responses during exercise in these patients. METHODS: Initially, were selected 78 patients with ACS with ejection fraction >= 45% at the time of hospitalization. One month after the ischemic event, 61 patients returned for the initial assessments. Patients were genotyped and then divided into two groups according to the Gln27Glu \'beta\'2-adrenoceptor polymorphisms: 1-Gln27Gln (CC, n=35) and 2-Gln27Glu + Glu27Glu (CG +GG, n=26). Of these, 29 patients agreed to participate in an exercise training protocol for a period of 8 weeks, but only 25 patients completed the protocol (CC, n=17; CG+GG, n=8). The evaluation of neurovascular control was performed at rest and during a handgrip exercise at 30% of the maximum voluntary contraction. We evaluated the MSNA, by the direct technique of microneurography, the FBF, by venous occlusion plethysmography technique, blood pressure (BP), by indirect oscillometric device and heart rate, by electrocardiogram. All evaluations were performed one month after the ischemic event and, for those patients subjected to the exercise training protocol the same evaluations were repeated after 8 weeks of intervention. RESULTS: One month after the ischemic event, the MSNA (P=0.26) and mean arterial pressure (MAP, P=0.14) at rest were similar between groups with genotype CC and CG+GG. However, during exercise, the response of MSNA was higher in the CC group compared with the CG+GG group (\'delta\'=11±2 vs. 4±2 bursts/100HB, P=0.02). In addition, BP response during exercise was higher in the CC group compared to the CG + GG group (\'delta\' =24 ±2 vs. 18±2 mmHg, P=0.04). The forearm vascular conductance (FVC) response during exercise was similar in both groups. After exercise training, baseline MSNA decreased in the group with CC genotype (63± 3vs. 48±5 bursts/100HB, P <0.001) but not in the group with CG+GG genotypes (70±4 vs. 55±5 bursts/100HB, P =0.06). Similarly, exercise training decreases the level (P= 0.007) and the response of MSNA (\'delta\'= 12±2 vs. 5±2 bursts/100HB, P= 0.02) during exercise in the group with CC genotype but not in the CG+GG group (P= 0.10) and (\'delta\'=7±3 vs 7±3 bursts/100HB, P= 0.96), respectively. Exercise training did not change the levels of MAP and FVC, during exercise in both groups. However, in the post exercise training period, the CG+GG group had lower MAP response (P =0.01) and higher FVC (P =0.03) during exercise compared to the CC group. CONCLUSION: Patients with ACS, carrying the CC genotype of the \'beta\'2-adrenoceptor have increased MSNA response during physiological maneuver as exercise when compared with patients carrying the CG+GG genotype. Exercise training reverses this exacerbated response of MSNA in patients with CC genotype. These results suggest an increased cardiovascular risk in patients with ACS with CC genotype of the \'beta\'2-adrenoceptor. Furthermore, exercise training should be strongly recommended for patients with ACS, especially for those with the CC genotype