-Adrenoceptor in the Human Heart

b 3 -adrenoceptors are involved in metabolism, gut relaxation, and vascular vasodilation. However, their existence and role in the human heart have not been documented. We investigated the effects of several b -adrenoceptor agonists and antagonists on the mechanical properties of ventricular endomyocardial biopsies. In the presence of nadolol, a b 1 and b 2 -adrenoceptor antagonist, isoprenaline produced consistent negative inotropic effects. Similar negative inotropic effects also resulted from the action of b 3 -adrenoceptor agonists with an order of potency: BRL 37344 . SR 58611 < CL 316243 . CGP 12177. The dose-response curve to BRL 37344–decreasing myocardial contractility was not modified by pretreatment with nadolol, but was shifted to the right by bupranolol, a nonselective b -adrenoceptor antagonist. b 3 -adrenoceptor agonists also induced a reduction in the amplitude and an acceleration in the repolarization phase of the human action potential. b 3 -adrenoceptor transcripts were detected in human ventricle by a polymerase chain reaction assay. These results indicate that: ( a ) b 3 -adrenoceptors are present and functional in the human heart; and ( b ) these receptors are responsible for the unexpected negative inotropic effects of catecholamines and may be involved in pathophysiological mechanisms leading to heart failure. ( J. Clin. Invest. 1996. 98:556–562.)