Carvedilol blockade of α1- and β-adrenoceptor induced inotropic responses in rats with congestive heart failure

Abstract Carvedilol is a combined α 1 - and β-adrenoceptor antagonist. We investigated the ability of carvedilol to antagonize functional effects mediated through myocardial α 1 -adrenoceptors in failing vs. non-failing (sham-operated) control hearts and compared such antagonisms to those of myocardial β-adrenoceptors. Congestive heart failure was induced in Wistar rats by coronary artery ligation. Papillary muscles experiments were performed. Carvedilol antagonized inotropic effects mediated through myocardial α 1 -adrenoceptors with similar potencies in failing (p K i  = 7.7 (95%, CI; 7.4–8.0)) and sham-operated hearts (p K i  = 7.9 (95%, CI; 7.6–8.1)). The potency for the α 1 -adrenoceptors was 10–30-fold lower than that for the β-adrenoceptors. In failing hearts, the α 1 -adrenoceptor mediated response was similar in size to the attenuated β-adrenoceptor mediated inotropic response. The β-adrenoceptor mediated lusitropic effects were not, however, attenuated in failing compared to sham-operated hearts. A low degree of α 1 -adrenoceptor blockade in the myocardium may contribute to the beneficial effects of carvedilol in heart failure.