COMPARISON BETWEEN ALPHA-1 ADRENOCEPTOR-MEDIATED AND BETA-ADRENOCEPTOR-MEDIATED INOTROPIC COMPONENTS ELICITED BY NOREPINEPHRINE IN FAILING HUMAN VENTRICULAR MUSCLE

The purpose of our study was to investigate the inotropic response to the endogenous agonist norepinephrine mediated through alpha-1 adrenoc eptors and to compare this response to that mediated through beta-adre noceptors in failing human ventricular myocardium. We studied ex vivo the inotropic effect of norepinephrine in isometrically contracting tr abecular myocardium from both ventricles of explanted hearts. By study ing influence of appropriate adrenoceptor blockers, qualitative charac teristics of the inotropic response and sensitivity of the inotropic r esponse to cholinergic stimulation, it was revealed that norepinephrin e evoked both alpha-1 and beta adrenoceptor-mediated inotropic effects in failing human ventricle myocardium. Quantitatively the inotropic r esponses to norepinephrine varied markedly between preparations, but t he 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 s ystems to norepinephrine depending on etiology of heart failure and po ssibly also thyroid status was observed. It is concluded that norepine phrine evokes an alpha-1 adrenoceptor-mediated inotropic effect compar able to that evoked through the beta adrenoceptors in failing human ve ntricular myocardium, and that this alpha-1 adrenoceptor-mediated inot ropic effect may be of functional importance.