Pharmacological analyses of hydralazine-induced cardiac action in intact dogs and isolated, blood-perfused canine atria.

The effects of hydralazine (HYD) on heart rate and blood pressure in the intact dog and on atrial rate and contractile force in the isolated atrium were investigated. HYD (0.1-1 mg) injected into the sinus node artery produced double peaked positive inotropic and negative chronotropic effects in a dose-related manner. The initial positive inotropic and negative chronotropic responses were not affected by propranolol and atropine, respectively. The second positive inotropic response was inhibited by propranolol or reserpine, but it was not suppressed by imipramine or tetrodotoxin. When HYD (0.1-1 mg/kg) was administered intravenously to the donor dog, an initial increase followed by a decrease in blood pressure and an increase in heart rate were observed. In the isolated atrium, an increase in contractile force was induced. The increases of blood pressure and heart rate in the donor dog and the positive inotropic effect in the isolated atrium after HYD treatment were suppressed by reserpine. These results suggest that HYD has direct positive inotropic and negative chronotropic effects and indirect cardiac stimulating effects caused by a release of catecholamines from sympathetic nerve terminals, and that HYD-induced catecholamine release is not mediated by a tyramine-like action or via nerve excitation.