MECHANISM OF THE VASODILATORY ACTION OF NICORANDIL ON CORONARY CIRCULATION IN DOGS

Nicorandil possesses hybrid properties as a nitrate and a potassium (K) channel opener. We have previously reported that large coronary arteries responded to nicorandil at low plasma concentrations, while dilatation of small coronary arteries only occurred at higher plasma concentrations (above 200 ng/ml) in chronically instrumented dogs. In this study we examined the effects of intravenous nicorandil on epicardial coronary artery diameter (CoD) and coronary blood flow (CBF) in the absence and presence of glibenclamide, a K+ channel blocker, as well as the effects of nitroglycerin and cromakalim as reference drugs. The increase in CBF induced by nicorandil and cromakalim was significantly suppressed by glibenclamide. However, the increase in CoD induced by nicorandil and nitroglycerin was not suppressed by glibenclamide. These findings suggest that nicorandil-induced dilatation of the large coronary arteries was related to its nitrate action, while nicorandil-induced dilatation of the small coronary arteries was closely related to its effect as a K+ channel opener. In addition, the former response to nicorandil occurred at low concentrations, while the latter occurred at higher concentrations.