Downregulation of myocardial beta-adrenergic receptors. Receptor subtype selectivity.

Abstract

T he desensitization (loss of response) and downregulation (loss of receptors) of p-adrenergic receptors (,BAR) have been observed in several cardiac conditions, including certain forms of heart failure and hypertension. The inability of the failing heart to respond to inotropic agents such as catecholamines represents a major clinical problem. The downregulation of 131AR associated with certain forms of heart failure1 has been considered a consequence of the chronic high plasma catecholamine levels associated with this disorder.

Targeted disruption of the mouse beta1-adrenergic receptor gene: developmental and cardiovascular effects.

“…Finally, it is possible that mouse myocytes express low or physiologically nonfunctional levels of ,B2-ARs. Although 131-and 132-AR coexpression on rat myocytes has been observed (26), the areas of highest expression of ,32-ARs in the heart are thought to be in connective tissue and arterioles (7). Thus, whereas a number of studies have demonstrated chronotropic and inotropic responses to stimulation of cardiac (32-ARs in humans (5,10,27,28) and rats or dogs (12,13), cardiac 132-AR function in mice may be restricted primarily to connective tissue and blood vessels.…”

Desensitization and Selective Down-Regulation of Rat Cardiac β1-Adrenoceptors by Prolonged In Vivo Infusion of T-0509, a β1-Adrenoceptor Full Agonist

“…There is now a body of evidence indicating the differential regulation of cardiac 3AR subtypes by catecholamines (34). In explanted human hearts with dilated cardiomyopathy, ;31ARs are significantly and selectively more down-regulated than the r32-subtype (35,36).…”

β 2 -Adrenergic Receptor Overexpression Exacerbates Development of Heart Failure After Aortic Stenosis

“…1,3-5 ␤ 2 -AR density remains unchanged, but uncoupling of ␤ 2 -ARs has been reported. [1][2][3]5 Other related changes include reduction in stimulatory GTP-binding protein (G s ), [1][2][3] suppressed activity of adenylyl cyclase, 1,2 and upregulation of inhibitory G protein (G i ). 1,6 The significance of the changes to the ␤-adrenergic system in HF, however, is not clear.…”