Functional β3-adrenoceptor in the human heart

Abstract

β3-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 β- adrenoceptor agonists and antagonists on the mechanical properties of ventricular endomyocardial biopsies. In the presence of nadolol, a β1-and β2-adrenoceptor antagonist, isoprenaline produced consistent negative inotropic effects. Similar negative inotropic effects also resulted from the action of β3-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 β- adrenoceptor antagonist. β3-adrenoceptor agonists also induced a reduction in the amplitude and an acceleration in the repolarization phase of the human action potential. β3-adrenoceptor transcripts were detected in human ventricle by a polymerase chain reaction assay. These results indicate that: (a) β3-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.