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Title[redir]:
Upregulation of β3-Adrenoceptors and Altered Contractile Response to Inotropic Amines in Human Failing Myocardium | Circulation
Description:
Background—Contrary to β1- and β2-adrenoceptors, β3-adrenoceptors mediate a negative inotropic effect in human ventricular muscle. To assess their functional role in heart failure, our purpose was to compare the expression and contractile effect of β3-adrenoceptors in nonfailing and failing human hearts. Methods and Results—We analyzed left ventricular samples from 29 failing (16 ischemic and 13 dilated cardiomyopathic) hearts (ejection fraction 18.6±2%) and 25 nonfailing (including 12 innervated) explanted hearts (ejection fraction 64.2±3%). β3-Adrenoceptor proteins were identified by immunohistochemistry in ventricular cardiomyocytes from nonfailing and failing hearts. Contrary to β1-adrenoceptor mRNA, Western blot analysis of β3-adrenoceptor proteins showed a 2- to 3-fold increase in failing compared with nonfailing hearts. A similar increase was observed for Gαi-2 proteins that couple β3-adrenoceptors to their negative inotropic effect. Contractile tension was measured in electrically stimulated myocardial samples ex vivo. In failing hearts, the positive inotropic effect of the nonspecific amine isoprenaline was reduced by 75% compared with that observed in nonfailing hearts. By contrast, the negative inotropic effect of β3-preferential agonists was only mildly reduced. Conclusions—Opposite changes occur in β1- and β3-adrenoceptor abundance in the failing left ventricle, with an imbalance between their inotropic influences that may underlie the functional degradation of the human failing heart.
Title[redir]:
Upregulation of β3-Adrenoceptors and Altered Contractile Response to Inotropic Amines in Human Failing Myocardium | Circulation
Description:
Background—Contrary to β1- and β2-adrenoceptors, β3-adrenoceptors mediate a negative inotropic effect in human ventricular muscle. To assess their functional role in heart failure, our purpose was to compare the expression and contractile effect of β3-adrenoceptors in nonfailing and failing human hearts. Methods and Results—We analyzed left ventricular samples from 29 failing (16 ischemic and 13 dilated cardiomyopathic) hearts (ejection fraction 18.6±2%) and 25 nonfailing (including 12 innervated) explanted hearts (ejection fraction 64.2±3%). β3-Adrenoceptor proteins were identified by immunohistochemistry in ventricular cardiomyocytes from nonfailing and failing hearts. Contrary to β1-adrenoceptor mRNA, Western blot analysis of β3-adrenoceptor proteins showed a 2- to 3-fold increase in failing compared with nonfailing hearts. A similar increase was observed for Gαi-2 proteins that couple β3-adrenoceptors to their negative inotropic effect. Contractile tension was measured in electrically stimulated myocardial samples ex vivo. In failing hearts, the positive inotropic effect of the nonspecific amine isoprenaline was reduced by 75% compared with that observed in nonfailing hearts. By contrast, the negative inotropic effect of β3-preferential agonists was only mildly reduced. Conclusions—Opposite changes occur in β1- and β3-adrenoceptor abundance in the failing left ventricle, with an imbalance between their inotropic influences that may underlie the functional degradation of the human failing heart.
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Keywords {🔍}
hearts, human, failing, βadrenoceptor, heart, inotropic, nonfailing, crossref, pubmed, google, scholar, βadrenoceptors, effect, ventricular, patients, βadrenergic, figure, abundance, cardiac, failure, receptor, circulation, dilated, proteins, myocardium, ischemic, contractile, cardiomyopathic, negative, isoprenaline, stimulation, response, increased, enos, nondenervated, normal, department, school, gαi, brl, tissues, antibody, view, expression, observed, positive, agonist, tissue, article, gauthier,
Topics {✒️}
aha/asa scientific statements nrf2/β3-adrenoreceptor axis drives g-protein–coupled receptor kinases chimeric β3/β2-adrenergic receptor american heart association supplements download pdf nonspecific β1-β2-β3-agonist alpha-myosin heavy chain β-adrenergic receptor kinase jean-noël trochu hpsc-derived cardiac model universitat zu köln ethyl-amino]propyl] phenoxyacetate 067876 abstract cardiac inotropic state nonspecific β-adrenergic agonist local ethics committees desensitization-resistant β3-adrenoceptor22 red ™ aha nonspecific β-adrenoceptor agonist β3-preferential adrenergic agonist β-adrenergic blockers slows β3-adrenergic receptor mrna β-adrenergic receptor blockade β-adrenoceptor subtypes result nitric oxide inhibits human β3-adrenergic receptor main content advertisement human cardiac β3-adrenoceptor β1-adrenoceptor–overexpressing mice β1-adrenergic receptor mrna distinct β-adrenoceptor subtypes terms early stages saint-luc university hospital β-adrenergic-receptor density cumulative concentration-response curves international users arteriosclerosis rapid homologous desensitization enhancing β1-adrenoceptor signaling β-adrenergic signaling molecules product length β1-ar adenoviral-mediated gene transfer estradiol-independent mrna control β3-preferential adrenoceptor agonists heart failure stroke β-adrenergic inotropic responsiveness inhibited cardiac contractility human β3-adrenoceptor studied decreased β1-adrenoceptor mrna
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