Catecholamines, cardiac beta-adrenergic receptors, and heart failure.
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TLDR
It is shown that in human heart failure, as well as in several animal models, elevated circulating catecholamines lead, via various compensatory mechanisms, to decreased levels and functional activity of cardiac b1-adrenergic receptors (b1ARs) and thus to marked desensitization of the heart to inotropic b- adrenergic stimulation.Abstract:
It is now generally accepted that chronically elevated stimulation of the cardiac b-adrenergic system is toxic to the heart and that such stimulation may contribute to the pathogenesis of congestive heart failure of various causes. Administration of either b-adrenergic agonists or phosphodiesterase inhibitors has been shown to decrease survival of patients with chronic heart failure, even though they produce immediate and long-term hemodynamic benefits. 1 Moreover, in human heart failure, as well as in several animal models, elevated circulating catecholamines lead, via various compensatory mechanisms, to decreased levels and functional activity of cardiac b1-adrenergic receptors (b1ARs) and thus to marked desensitization of the heart to inotropic b-adrenergic stimulation.2read more
Citations
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Molecular distinction between physiological and pathological cardiac hypertrophy: experimental findings and therapeutic strategies.
Bianca C. Bernardo,Kate L. Weeks,Kate L. Weeks,Lynette Pretorius,Lynette Pretorius,Julie R. McMullen +5 more
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References
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Journal ArticleDOI
The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial
TL;DR: Beta-blocker therapy had benefits for survival in stable heart-failure patients and should not be extrapolated to patients with severe class IV symptoms and recent instability because safety and efficacy has not been established in these patients.
Journal ArticleDOI
G protein-coupled receptor kinases.
TL;DR: This review focuses on the regulation of GRK activity by a variety of allosteric and other factors: agonist-stimulated GPCRs, beta gamma subunits of heterotrimeric GTP- binding proteins, phospholipid cofactors, the calcium-binding proteins calmodulin and recoverin, posttranslational isoprenylation and palmitoylation, autophosphorylation, and protein kinase C-mediated GRK phosphorylation.
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Switching of the coupling of the beta2-adrenergic receptor to different G proteins by protein kinase A.
TL;DR: A mechanism previously shown to mediate uncoupling of the β2-adrenergic receptor from Gs and thus heterologous desensitization (PKA-mediated receptor phosphorylation), also serves to ‘switch’ coupling of this receptor fromGs to Gi and initiate a new set of signalling events.
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Progressive hypertrophy and heart failure in beta1-adrenergic receptor transgenic mice.
TL;DR: It is concluded that overexpression of beta1-adrenergic receptors in the heart may lead to a short-lived improvement of cardiac function, but that increasedbeta1- adrenergic receptor signalling is ultimately detrimental.
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Enhanced myocardial function in transgenic mice overexpressing the beta 2-adrenergic receptor
Carmelo A. Milano,Lee F. Allen,Howard A. Rockman,Paul C. Dolber,T. R. McMinn,Kenneth R. Chien,T. D. Johnson,Richard A. Bond,Robert J. Lefkowitz +8 more
TL;DR: Transgenic mice were created with cardiac-specific overexpression of the beta 2-adrenergic receptor that resulted in increased basal myocardial adenylyl cyclase activity, enhanced atrial contractility, and increased left ventricular function in vivo, suggesting a potential gene therapy approach to this disease state.