GLIBENCLAMIDE, A PUTATIVE ATP-SENSITIVE K+ CHANNEL BLOCKER, INHIBITS CORONARY AUTOREGULATION IN ANESTHETIZED DOGS

We tested the hypothesis that ATP-sensitive K+ channels are involved i n the mechanism mediating coronary autoregulation in open-chest dogs. We perfused the left anterior descending coronary artery with arterial blood from an extracorporeal circuit and measured steady-state corona ry blood flow (CBF) with stepwise changes in coronary perfusion pressu re (CPP) between 50 and 150 mm Hg during an intracoronary infusion of vehicle or glibenclamide (a putative blocker of ATP-sensitive K+ chann els). CBF was relatively stable over CPP between 50 and 110 mm Hg duri ng vehicle infusion, indicating the presence of autoregulation at the CPP range. During glibenclamide infusion (10 mug . min-1 . kg-1), CBF progressively decreased with reduction in CPP below 110 mm Hg, whereas the CPP-CBF relation at CPP above 110 mm Hg was not altered by gliben clamide. The autoregulation index [1-(DELTAF/F)/(DELTAP/P), where F in dicates CBF and P indicates CPP] was greater than 0 over the CPP range between 50 and 100 mm Hg during vehicle infusion and was less than 0 during glibenclamide infusion. Glibenclamide did not after systemic ar terial pressure, heart rate, left ventricular pressure, and changes in regional myocardial oxygen consumption associated with changes in CPP . In the absence of glibenclamide, the CPP-CBF relation was reproducib le in the repeated studies for time control. These results suggest tha t ATP-sensitive K+ channels play an important role in mediating corona ry autoregulation at the lower range of CPP in the blood-perfused dog heart.