Beta3-Adrenergic Receptors in Cardiac and Vascular Tissues

Pole of Pharmacology and Therapeutics, Institute of Experimental and Clinical Research, Université catholique de Louvain, Brussels, Belgium.
Advances in pharmacology (San Diego, Calif.) 12/2010; 59(C):135-63. DOI: 10.1016/S1054-3589(10)59005-7
Source: PubMed


Catecholamines released by the orthosympathetic system play a major role in the short- and long-term regulation of cardiovascular function. Beta1- and beta2-adrenoreceptors (ARs) have classically been considered as mediating most of their effects on cardiac contraction. After their initial cloning and pharmacologic characterization in the late 1980s, beta3-ARs have been mostly thought of as receptors mediating metabolic effects (e.g., lipolysis) in adipocytes. However, definitive evidence for their expression and functional coupling in cardiovascular tissues (including in humans) has recently initiated a re-examination of their implication in the pathophysiology of cardiovascular diseases. Distinctive pharmacodynamic properties of beta3-AR, e.g., their upregulation in disease and resistance to desensitization, suggest that they may be attractive targets for therapeutic intervention. They may substitute efficient vasodilating pathways when beta1/2-ARs are inoperative. In the heart, their contractile effects, which are functionally antipathetic to those of beta1/2-AR, may protect the myocardium against adverse effects of excessive catecholamine stimulation and perhaps mediate additional ancillary effects on key aspects of electrophysiology or remodeling. Longitudinal studies in animals and patients with different stages of heart failure are now needed to identify the optimal therapeutic scheme using specific combinations of agonists or antagonists at all three beta-ARs.

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    • "Thus, adrenergic receptors are important regulators of cardiovascular physiology. Although all three beta adrenergic receptor (β-AR) subtypes, β1, β2, and β3, are found in vascular smooth muscle cells, the β2-AR subtype is by far the most highly expressed [6]. Of specific relevance to this paper is that the vascular β2-AR exhibits an age-related decline in signaling with advancing age that leads to impaired vasorelaxation. "
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    ABSTRACT: Catecholamines play a key role in the regulation of cardiovascular function, classically through ß(1/2)-adrenoreceptors (AR) activation. After ß(3)-AR cloning in the late 1980s, convincing evidence for ß(3)-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 ß(1/2)-AR to mediate vasodilation in diabetic or atherosclerotic vessels. In cardiac ventricle, their contractile effects are functionally antipathetic to those of ß(1/2)-AR; in normal heart, ß(3)-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 ß(3)-AR agonists and/or antagonists.
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