Carvedilol blockade of rat myocardial alpha1-adrenoceptors |
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Authors: | Qvigstad Eirik Osnes Jan Bjørn Sandnes Dagny Schiander Iwona Bøkenes Janny Sjaastad Ivar Skomedal Tor |
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Affiliation: | Department of Pharmacology, University of Oslo, P.O. Box 1057 Blindern, N-0316 Oslo, Norway. eirik.qvigstad@labmed.uio.no |
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Abstract: | Carvedilol is a combined alpha(1)- and beta-adrenoceptor antagonist. The ability of carvedilol to antagonize functional effects mediated through myocardial alpha(1)-adrenoceptors has never been investigated. We tested the ability of carvedilol to antagonize the inotropic effect mediated by myocardial alpha(1)-adrenoceptors compared to the antagonism of beta-adrenoceptors. Papillary muscles from rat heart left ventricle were mounted in an organ bath and concentration-response experiments for the inotropic effects of separate alpha(1)- and beta-adrenoceptor stimulation were performed in the absence and presence of carvedilol. Carvedilol antagonized myocardial alpha(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 beta-adrenoceptor stimulation revealed a K(i) of 1.2+/-0.35 nmol/l. Thus, carvedilol antagonizes the myocardial alpha(1)-adrenoceptors with a 9-fold lower potency than the beta-adrenoceptors. Antagonism of myocardial alpha(1)-adrenoceptor evoked effects may contribute to clinical effects of carvedilol. |
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Keywords: | Carvedilol α1-Adrenoceptor β-Adrenoceptor Myocardium, rat |
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