GLIBENCLAMIDE DECELERATES THE RESPONSES OF CORONARY REGULATION IN THEGOAT

The role of blocking ATP-sensitive potassium (K-ATP) channels by glibe nclamide on the dynamic responses of coronary resistance to abrupt cha nges in perfusion pressure and heart rate was investigated. The left m ain coronary artery of the open-chest anesthetized goat was perfused w ith constant pressure (P-p). P-p and arterial flow were averaged per b eat, and their ratio was calculated as index of coronary resistance. R esponses of resistance index after heart rate (HR) and P-p changes bef ore and after administration of glibenclamide were compared. Their rat e of change was quantified by t(50), the required time to obtain half of the complete response. During control, t(50) for the dilating respo nse induced by a decrease in P-p or increase in HR was 3.8 +/- 0.2 and 6.2 +/- 0.5 (SE) s, respectively. With glibenclamide these values wer e 24.4 +/- 1.6 and 14.9 +/- 2.1 s. For the constricting response, the numbers for control were 5.8 +/- 0.3 (increase P-p) and 7.2 +/- 0.8 (d ecrease HR) s. With glibenclamide these values were 22.1 +/- 1.5 and 1 6.0 +/- 2.9 s. The steady-state adjustment of coronary flow was not al tered by glibenclamide. It was concluded that glibenclamide has a mino r effect on coronary flow control but reduces the rate of change of co ronary resistance index up to a factor of four. Because glibenclamide is supposed to act on K-ATP channels, it may be concluded that these c hannels play a major role in the dynamics of coronary blood flow regul ation.