CARDIOPROTECTIVE EFFECTS OF NICORANDIL ON ISOPROTERENOL-INDUCED INJURY

Nicorandil, a new anti-anginal drug, exerts a coronary vasodilation effect by mechanisms different from either nitrates or slow channel Ca++ entry blockers. This agent has been demonstrated to increase membrane K+ conductance, elevate cyclic guanosine monophosphate content, and inhibit Ca++ kinetics in vascular smooth muscle cells. In the myocardium, however, the direct effects of the agent have not been elucidated. We examined whether nicorandil could antagonize myocardial injury in chick hearts induced by a toxic dose of isoproterenol. Isoproterenol treatment (240 mg/kg subcutaneously twice a day for 4 days) caused a significant increase in heart/body weight ratio and induced a remarkable histological perturbation. A substantial accumulation of Ca++ and a profound decrease of creatine kinase and lactate dehydrogenase activity were observed in the myocardium from isoproterenol-treated chick. Oral administration of nicorandil (4 mg/day for 4 days, 15 min prior to each isoproterenol treatment) attenuated the deterioration induced by isoproterenol. The present study suggests that nicorandil partially protects the myocardium from the isoproterenol-induced injury.