Komaru T, Lamping K G, Eastham C L, Dellsperger K C
Department of Internal Medicine, College of Medicine, University of Iowa, Iowa City 52242.
Circ Res. 1991 Oct;69(4):1146-51. doi: 10.1161/01.res.69.4.1146.
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.
ATP敏感性钾通道介导体内冠状动脉小动脉的自动调节性血管舒张。实验在23只开胸麻醉犬身上进行。使用活体显微镜和与心动周期同步的频闪落射照明，通过荧光微血管造影术直接测量冠状动脉微血管直径。在左前降支冠状动脉周围放置封堵器，在有或没有格列本脲（10⁻⁵ M，局部应用）（其抑制ATP敏感性钾通道）或赋形剂的情况下，造成轻度冠状动脉狭窄（灌注压 = 60 mmHg）、重度冠状动脉狭窄（灌注压 = 40 mmHg）和完全冠状动脉闭塞。在局部应用赋形剂（0.01%二甲亚砜）期间，在灌注压降低时小（直径小于100微米）动脉出现扩张（直径变化百分比：在轻度狭窄、重度狭窄和完全闭塞时分别为6.7±1.5%、11.7±3.5%和10.4±5.1%）。在有格列本脲存在的情况下，冠状动脉狭窄和闭塞期间的小动脉扩张被消除。格列本脲不影响直径大于100微米的小动脉的反应。格列本脲不改变微血管对硝普钠的反应。这些数据表明，ATP敏感性钾通道在决定冠状动脉微血管对灌注压降低的反应中起重要作用。
