Beta-3 Adrenoceptors as New Therapeutic Targets for Cardiovascular Pathologies
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Catecholamines play a key role in the regulation of cardiovascular function, classically through ß1/2-adrenoreceptors (AR) activation. After ß3-AR cloning in the late 1980s, convincing evidence for ß3-AR expression and function in cardiovascular tissues recently initiated a reexamination of their involvement in the pathophysiology of cardiovascular diseases. Their upregulation in diseased cardiovascular tissues and resistance to desensitization suggest they may be attractive therapeutic targets. They may substitute for inoperant ß1/2-AR to mediate vasodilation in diabetic or atherosclerotic vessels. In cardiac ventricle, their contractile effects are functionally antipathetic to those of ß1/2-AR; in normal heart, ß3-ARs may mediate a moderate negative inotropic effect, but in heart failure, it may protect against adverse effects of excessive catecholamine stimulation by action on excitation-contraction coupling, electrophysiology, or remodelling. Thus, prospective studies in animals and patients at different stages of heart failure should lead to identify the best therapeutic window to use ß3-AR agonists and/or antagonists.
Keywordsß3-adrenoceptor Adrenergic receptor ß-blocker Heart Vessels Nitric oxide Nitric oxide synthase NO NOS Remodeling Electrophysiology Contractility Heart failure Hypertension Diabetes Myocardial infarction Diabetes Catecholamine Nebivolol Cyclic guanosine monophosphate cGMP Cyclic adenosine monophosphate cAMP Messenger RNA mRNA Ventricular remodeling Cardiomyocytes Excitation-contraction coupling
Work supported by grants from the Federation Française de Cardiologie, the Fondation de France and Association Française contre les Myopathies (AFM)to CG and by grants from the Fonds National de la Recherche Scientifique, the Fondation Leducq, Politique Scientifique Fédérale (PAI P6/30) and Communauté Française de Belgique (ARC) to JLB.
No potential conflicts of interest relevant to this article were reported.
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