TY - JOUR T1 - Comparison between <em>Alpha</em>-1 Adrenoceptor-Mediated and <em>Beta</em> Adrenoceptor-Mediated Inotropic Components Elicited by Norepinephrine in Failing Human Ventricular Muscle JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 721 LP - 729 VL - 280 IS - 2 AU - Tor Skomedal AU - Kjell Borthne AU - Halfdan Aass AU - Odd Geiran AU - Jan-Bjørn Osnes Y1 - 1997/02/01 UR - http://jpet.aspetjournals.org/content/280/2/721.abstract N2 - The purpose of our study was to investigate the inotropic response to the endogenous agonist norepinephrine mediated throughalpha-1 adrenoceptors and to compare this response to that mediated through beta-adrenoceptors in failing human ventricular myocardium. We studied ex vivo the inotropic effect of norepinephrine in isometrically contracting trabecular myocardium from both ventricles of explanted hearts. By studying influence of appropriate adrenoceptor blockers, qualitative characteristics of the inotropic response and sensitivity of the inotropic response to cholinergic stimulation, it was revealed that norepinephrine evoked both alpha-1 andbeta adrenoceptor-mediated inotropic effects in failing human ventricle myocardium. Quantitatively the inotropic responses to norepinephrine varied markedly between preparations, but the mean responses elicited through the respective adrenoceptor systems were of comparable magnitude. Concomitant stimulation of alpha-1 and beta adrenoceptors by norepinephrine alone revealed a contribution of an alpha-1 adrenoceptor-mediated component to the final and unopposed inotropic response. Differential sensitivity of the two adrenoceptor systems to norepinephrine depending on etiology of heart failure and possibly also thyroid status was observed. It is concluded that norepinephrine evokes analpha-1 adrenoceptor-mediated inotropic effect comparable to that evoked through the beta adrenoceptors in failing human ventricular myocardium, and that thisalpha-1 adrenoceptor-mediated inotropic effect may be of functional importance. The American Society for Pharmacology and Experimental Therapeutics ER -