VASODILATORY EFFECT OF NICORANDIL ON CORONARY ARTERIAL MICROVESSELS - ITS DEPENDENCY ON VESSEL SIZE AND THE INVOLVEMENT OF THE ATP-SENSITIVE POTASSIUM CHANNELS

We aimed to clarify the size dependency of nicorandil-induced dilation in coronary microcirculation and the involvement of adenosine triphosphate (ATP)-sensitive potassium channels. Coronary arterial microvessels were observed through a microscope equipped with a floating objective in anesthetized open-chest dogs (n = 29). Heart rate and mean aortic pressure were maintained at control level. In 16 dogs, nicorandil was infused into the coronary in a cumulative fashion (0.1, 1.0, 10, and 100 mu g/kg/min, for 5 min for each dose). In 13 dogs, glibenclamide (10 mu M) was topically applied onto the observed area, and nicorandil was similarly infused. Nicorandil dilated vessels <100 mu m in diameter at all applied doses in a dose-dependent manner. Glibenclamide abolished the dilation of these vessels at the lower two doses. Vessels >100 mu m in diameter dilated only at the two higher doses and the dilation was not affected by glibenclamide. These data suggest that the vessels <100 mu m are more sensitive to this agent than other size vessels, and that ATP-sensitive potassium channels are involved in the nicorandil-induced dilation of vessels smaller than 100 mu m, whereas the dilation of other size vessels occurs independently of this channel.