Hyperresponsiveness of Cardiac Muscles to Histamine in Reserpine-Treated Guinea Pigs

The hyperresponsiveness of cardiac tissue to histamine following treatment with reserpine was pharmacologically characterized. Guinea pig hearts were isolated 24 hours after intraperitoneal administration of 5 mg/kg reserpine. This treatment resulted in a complete depletion of tissue norepinephrine. Reserpine treatment potentiated the positive inotropic response of isolated perfused hearts to histamine at doses ranging from 0.3 to 3 micrograms (23 to 57% increase for reserpine-treated animals vs. 14 to 32% increase for control animals). Isolated left ventricular papillary muscle of reserpine-treated guinea pig hearts also showed hyperresponsiveness to histamine at concentrations of 0.1 microM or greater. The hyperresponsiveness of the papillary muscle contraction of the reserpine-treated animals to histamine was abolished in the presence of 1 microM cimetidine, but not attenuated in the presence of 1 microM diphenhydramine. This hyperresponsiveness was not modified by 1 microM bunazosin or 1 microM propranolol. The results suggest that H2-receptor mediated action plays a role in the hyperresponsiveness of cardiac muscles to histamine.