EFFECT OF AN ATP-SENSITIVE POTASSIUM CHANNEL OPENER, LEVCROMAKALIM, ON CORONARY ARTERIAL MICROVESSELS IN THE BEATING CANINE HEART

Objective: The aim was to clarify the site in the coronary microcircul ation that is dilated by an ATP sensitive potassium channel opener, le vcromakalim, and to examine whether the magnitude of dilatation is siz e dependent. Methods: Coronary arterial microvessels were observed thr ough an intravital microscope equipped with a floating objective in be ating canine left ventricles in situ. Flow velocity of the left anteri or descending coronary artery was measured with a suction-type Doppler probe. Heart rate and aortic pressure were maintained at control leve ls throughout the experiments. Three doses of levcromakalim (0.01-1.0 mu g.kg(-1).min(-1)) or a single dose (1.0 mu g.k(-1).min(-1)) were in fused into the coronary artery in groups, with or without intracoronar y glibenclamide pretreatment (200 or 400 mu g.kg(-1)). The effect of l evcromakalim on different sized vessels was assessed by dividing them into three groups according to control diameter (small, internal diame ter <100 mu m; medium, greater than or equal to 100, <200 mu m; large, greater than or equal to 200 mu m). Results: The lowest dose of levcr omakalim dilated only the small vessels. The two higher doses dilated Vessels of all sizes, but the magnitude of dilatation was greater in t he small vessel soup than in the other two groups. Coronary resistance significantly decreased dose dependently during the infusion of 0.1 a nd 1.0 mu g.kg(-1).min(-1) of levcromakalim. Pretreatment with glibenc lamide markedly attenuated the levcromakalim induced dilatation of all vessel groups and the reduction in coronary Vascular resistance. Conc lusions: Levcromakalim heterogeneously dilates coronary arterial micro vessels via the opening of ATP sensitive potassium channels, and small vessels are more sensitive to levcromakalim.