Effects of a new antianginal agent, nicorandil, on the cardiovascular system of the miniature pig: with special reference to coronary vasospasm.

The cardiovascular and vasospasmolytic effects of a newly developed nicotinamide derivative, N-(2-hydroxyethyl)nicotinamide nitrate(ester) (nicorandil), were examined in anesthetized, open-chest "miniature" pigs, and compared with those of nitroglycerin. Nicorandil, administered i.v. in doses of 10 micrograms/kg to 1 mg/kg, decreased systemic blood pressure, left ventricular (LV) systolic pressure, pressure rate product and coronary and femoral vascular resistance. It pronouncedly increased coronary blood flow and slightly increased heart rate. An increase, often preceded by a decrease, occurred in the LVdP/dt max. In doses of 10 to 100 micrograms/kg, nicorandil induced a slight increase followed by a decrease in femoral blood flow, but larger doses always decreased it. Similar results were obtained with nitroglycerin for all the cardiovascular parameters tested except LVdP/dt max and coronary blood flow. Unlike nicorandil, nitroglycerin induced a decrease often preceded by an increase in the LVdP/dt max. In doses of 1 to 30 micrograms/kg, nitroglycerin caused a decrease preceded by a slight and transient increase in the coronary blood flow. Nicorandil, administered i.v. in doses of 30 micrograms/kg to 1 mg/kg, inhibited coronary vasoconstriction caused by methacholine (3 or 10 micrograms) and norepinephrine (2-4 micrograms in the presence of propranolol) injected directly into the coronary artery. The magnitude and duration of this antagonism depended on the dose of nicorandil used. Although nitroglycerin in a dose of 10 or 30 micrograms/kg also effectively inhibited coronary vasoconstrictor responses to the two vasoactive agents, dipyridamole (60 micrograms/kg) failed to do so. Thus, nicorandil has prominent vasospasmolytic effects and is an efficacious coronary vasodilator which reduces afterload.