Glibenclamide decreases basal coronary blood flow in anesthetized dogs

The effects of ATP-sensitive K+ channel blockade on coronary blood flow were studied in 13 anesthetized open-chest dogs. A specific ATP-sensitive K+ channel blocker, glibenclamide, was infused into the left circumflex coronary artery (LCx). Coronary blood flow of LCx and systolic segment shortening at the LCx area were measured. Intracoronary infusion of glibenclamide (0.5, 5, and 50 micrograms.kg-1.min-1) decreased coronary blood flow dose dependently. Glibenclamide at the dose of 50 micrograms.kg-1.min-1 decreased LCx coronary blood flow by 55 +/- 4% (P less than 0.01), which was accompanied by a decrease in percentage segment shortening at the LCx area (P less than 0.01) and ST elevation. When coronary blood flow was maintained at the baseline level by simultaneous infusion of sodium nitroprusside (1-3 micrograms/min ic) or pinacidil (0.3-0.6 mg/min ic), glibenclamide did not alter percentage segment shortening or produced ST elevation. The latter results suggest that glibenclamide decreased coronary blood flow, which secondarily induced myocardial ischemia and dysfunction. Our results suggest that ATP-sensitive K+ channels of coronary arteries are involved in maintaining the level of resting coronary blood flow under physiological conditions in anesthetized dogs.