Histamine attenuates the arrhythmogenic effects of norepinephrine in hearts of spontaneously hypertensive rats

Abstract

A potential physiological role for cardiac histamine and its interaction with norepinephrine were investigated in isolated left ventricles from spontaneously hypertensive rats (SHR). Prior to drug administration, left ventricle-to-body weight ratios and spontaneous firing rates (beats per min) were significantly increased in SHR ventricles vs. age- and sex-matched controls (WKY). Also, action potential duration was significantly prolonged in SHR at all levels of repolarization. In all hearts, norepinephrine (10(-7)-10(-4) M) increased spontaneous rate and the percent incidence of arrhythmias. The H2-receptor antagonist cimetidine (10(-5) M) potentiated the rate and arrhythmogenic effects of norepinephrine in SHR and, to a lesser extent, in WKY preparations; propranolol (10(-6) M) reduced them. Histamine (10(-7) M) also inhibited the norepinephrine-induced increase in arrhythmias in SHR, but not in WKY. The attenuation of adrenergically induced rhythm disturbances by histamine and their potentiation by cimetidine in hypertensive hearts support the hypothesis that histamine plays a role as a postjunctional modulator of adrenoceptor function in a setting of hypertension and myocardial hypertrophy.