DIFFERENTIAL-EFFECTS OF NITROVASODILATORS, K+ -CHANNEL OPENERS, AND NICORANDIL ON LARGE AND SMALL CORONARY-ARTERIES IN CONSCIOUS DOGS

When administered intravenously to conscious dogs, nicorandil, nitrovasodilators (nitroglycerin and SIN-1), and the K+-channel opener cromakalim exhibited marked differential effects on large epicardial and small resistance coronary arteries. Nitrovasodilators markedly increased the left circumflex coronary artery diameter at doses at which coronary resistance was not significantly decreased. In contrast, both cromakalim and nicorandil dilated large and small coronary arteries in the same conditions. When coronary blood flow was held to its control value by partial inflation of a hydraulic occluder implanted around the artery, the nitroglycerin- and nicorandil-induced increases in large coronary diameter remained unchanged whereas the response to cromakalim was reduced significantly. This coronary dynamic profile indicates that both nitrovasodilators and nicorandil directly dilate large coronary vessels, whereas the effect of cromakalim on these vessels is mediated partially through a flow-dependent mechanism. This suggests that nicorandil mainly dilates large coronary arteries through its nitroglycerin-like properties, whereas its ability to dilate coronary resistance vessels depends mainly on its K+-channel opener-like properties.