Topical glibenclamide abolished the dilatation of small coronary arterioles (<100 microns) in response to reductions in perfusion pressure compared to vehicle in anesthetized dogs.
Does glibenclamide alter coronary microvascular autoregulatory responses to reductions in perfusion pressure in open-chest anesthetized dogs?
ATP-sensitive potassium channels play an important role in mediating autoregulatory vasodilatation of coronary arterioles during reductions in perfusion pressure.
The purpose of the present study was to test the hypothesis that ATP-sensitive potassium channels mediate autoregulatory vasodilatation of coronary arterioles in vivo. Experiments were performed in 23 open-chest anesthetized dogs. Coronary arterial microvascular diameters were directly measured with fluorescence microangiography using an intravital microscope and stroboscopic epi-illumination synchronized to the cardiac cycle. A mild coronary stenosis (perfusion pressure = 60 mm Hg), a critical coronary stenosis (perfusion pressure = 40 mm Hg), and complete coronary artery occlusion were produced with an occluder around the left anterior descending coronary artery in the presence or absence of glibenclamide (10(-5) M, topically), which inhibits ATP-sensitive potassium channels, or of vehicle. During topical application of vehicle (0.01% dimethyl sulfoxide), there was dilatation of small (less than 100 microns diameter) arterioles during reductions in perfusion pressure (percent change in diameter: 6.7 +/- 1.5%, 11.7 +/- 3.5%, and 10.4 +/- 5.1% during mild stenosis, critical stenosis, and complete occlusion, respectively). In the presence of glibenclamide, arteriolar dilatations during coronary stenoses and occlusions were abolished. Glibenclamide did not affect responses of arterioles greater than 100 microns. Glibenclamide did not alter microvascular responses to nitroprusside. These data suggest that ATP-sensitive potassium channels play an important role in determining the coronary microvascular response to reductions in perfusion pressure.
Komaru et al. (1991) studied this question. Glibenclamide vs. Vehicle (0.01% dimethyl sulfoxide) was evaluated on Arteriolar dilatations during coronary stenoses and occlusions. Topical glibenclamide abolished the dilatation of small coronary arterioles (<100 microns) in response to reductions in perfusion pressure compared to vehicle in anesthetized dogs.