Nicorandil releases acetylcholine-induced sustained coronary arterial constriction in monkeys and baboons

The spasmolytic action of nicorandil on coronary circulation was investigated in 3 Japanese monkeys (Macaca fuscata), 1 rhesus monkey (Macaca mulatta), and 1 anubis baboon (Papio anubis) anesthetized with pentobarbital. The arterial bed of the left anterior descending coronary artery (LAD) was perfused with autologous arterial blood at a constant pressure close to systolic arterial blood pressure. Single injections of nicorandil (10-300 micrograms) into the LAD produced a dose-dependent increase in blood flow without affecting either systemic arterial blood pressure or heart rate. With continuous infusion of acetylcholine into the LAD, the LAD flow decreased to nearly half the basal level, indicating sustained coronary arterial constriction. Under these conditions intra-LAD nicorandil increased the LAD flow virtually to the same extent as before acetylcholine-infusion. These effects of nicorandil resemble those of the Ca++-antagonists, diltiazem and nifedipine, but differ from those of nitroglycerin, which is less effective during sustained coronary arterial constriction. The results imply that nicorandil may be as effective as Ca++-antagonists in the treatment of vasospastic angina.