Carvedilol blockade of rat myocardial α1-adrenoceptors

Abstract Carvedilol is a combined α 1 - and β-adrenoceptor antagonist. The ability of carvedilol to antagonize functional effects mediated through myocardial α 1 -adrenoceptors has never been investigated. We tested the ability of carvedilol to antagonize the inotropic effect mediated by myocardial α 1 -adrenoceptors compared to the antagonism of β-adrenoceptors. Papillary muscles from rat heart left ventricle were mounted in an organ bath and concentration–response experiments for the inotropic effects of separate α 1 - and β-adrenoceptor stimulation were performed in the absence and presence of carvedilol. Carvedilol antagonized myocardial α 1 -adrenoceptors with an inhibition constant ( K i ) of 11.0±3.0 nmol/l and the functional experiments were supported by radioligand-binding studies. Corresponding functional studies on the response to β-adrenoceptor stimulation revealed a K i of 1.2±0.35 nmol/l. Thus, carvedilol antagonizes the myocardial α 1 -adrenoceptors with a 9-fold lower potency than the β-adrenoceptors. Antagonism of myocardial α 1 -adrenoceptor evoked effects may contribute to clinical effects of carvedilol.