Functional beta(3)-adrenoceptor in the human heart

beta(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 beta-adrenoceptor agonists and antagonists on the mechanical properties of ventricular endomyocardial biopsies. In the presence of nadolol, a beta(1)- and beta(2)-adrenoceptor antagonist, isoprenaline produced consistent negative inotropic effects. Similar negative inotropic effects also resulted from the action of beta(3)-adrenoceptor agonists with an order of potency: BRL 37344 > SR 58611 approximate to 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 beta-adrenoceptor antagonist. beta(3)-adrenoceptor agonists also induced a reduction in the amplitude and an acceleration in the repolarization phase of the human action potential, beta(3)-adrenoceptor transcripts were detected in human ventricle by a polymerase chain reaction assay. These results indicate that: (a) beta(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.