Comparison between Alpha-1 Adrenoceptor-Mediated and Beta Adrenoceptor-Mediated Inotropic Components Elicited by Norepinephrine in Failing Human Ventricular Muscle 1
ABSTRACT The purpose of our study was to investigate the inotropic response to the endogenous agonist norepinephrine mediated through alpha-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 and beta 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 an alpha-1 adrenoceptor-mediated inotropic effect comparable to that evoked through the beta adrenoceptors in failing human ventricular myocardium, and that this alpha-1 adrenoceptor-mediated inotropic effect may be of functional importance. The catecholamine-induced increase in contractile force in mammalian myocardium is mainly due to activation of beta adrenoceptors. The existence of myocardial alpha-1 adrenoceptors mediating positive inotropic effects is, however, now well established In the failing human heart where the beta-1 adrenoceptor mediated inotropic response is attenuated, it has been difficult to demonstrate an alpha-1 adrenoceptor-mediated inotropic effect of functional significance (e.g.
