GLIBENCLAMIDE DECELERATES THE RESPONSES OF CORONARY REGULATION IN THE GOAT

The role of blocking ATP-sensitive potassium (K-ATP) channels by glibenclamide on the dynamic responses of coronary resistance to abrupt changes in perfusion pressure and heart rate was investigated. The left main coronary artery of the open-chest anesthetized goat was perfused with constant pressure (P-p). P-p and arterial flow were averaged per beat, and their ratio was calculated as index of coronary resistance. Responses of resistance index after heart rate (HR) and P-p changes before and after administration of glibenclamide were compared. Their rate of change was quantified by t(50), the required time to obtain half of the complete response. During control, t(50) for the dilating response 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 were 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 (decrease HR) s. With glibenclamide these values were 22.1 +/- 1.5 and 16.0 +/- 2.9 s. The steady-state adjustment of coronary flow was not altered by glibenclamide. It was concluded that glibenclamide has a minor effect on coronary flow control but reduces the rate of change of coronary resistance index up to a factor of four. Because glibenclamide is supposed to act on K-ATP channels, it may be concluded that these channels play a major role in the dynamics of coronary blood flow regulation.