Glibenclamide decelerates the responses of coronary regulation in the goat
Dankelman, J.; Van der Ploeg, C.P.; Spaan, J.A.
American Journal of Physiology 266(5 Pt 2): H1715-H1721
1994
ISSN/ISBN: 0002-9513 PMID: 8203571 Document Number: 426953
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.