钾离子ATP通道在运动时冠状动脉舒张中的作用。

Role of K+ATP channels in coronary vasodilation during exercise.

作者信息

Duncker D J, Van Zon N S, Altman J D, Pavek T J, Bache R J

机构信息

Department of Medicine, University of Minnesota Medical School, Minneapolis 55455.

出版信息

Circulation. 1993 Sep;88(3):1245-53. doi: 10.1161/01.cir.88.3.1245.

DOI:10.1161/01.cir.88.3.1245

PMID:8353886

Abstract

BACKGROUND

The mechanism of metabolic regulation of coronary vascular tone is still unclear. Therefore, we examined the role of vascular smooth muscle K+ATP channels in regulating coronary blood flow under resting conditions, during increments in myocardial metabolic demand produced by treadmill exercise, and in response to a brief ischemic stimulus.

METHODS AND RESULTS

Ten chronically instrumented dogs were studied at rest and during a four-stage exercise protocol under control conditions and during intracoronary infusion of the K+ATP channel blocker glibenclamide at rates of 10 and 50 micrograms.kg-1 x min-1. Glibenclamide (50 micrograms.kg-1 x min-1) decreased coronary blood flow at rest from 51 +/- 4 to 42 +/- 6 mL/min (P < .05), decreased myocardial oxygen consumption from 5.70 +/- 0.31 to 4.11 +/- 0.56 mL O2/min (P < .05), and decreased systolic wall thickening from 21 +/- 3% to 12 +/- 3% (P < .05). The depression of systolic wall thickening produced by glibenclamide was reversed when coronary blood flow was restored to the control level with intracoronary nitroprusside, indicating a primary effect of glibenclamide on coronary flow during resting conditions. However, glibenclamide did not impair the increases of coronary blood flow, myocardial oxygen consumption, and systolic wall thickening that occurred during exercise. In eight resting awake dogs, 50 micrograms.kg-1 x min-1 glibenclamide decreased the peak reactive hyperemia blood flow rate following a 20-second coronary occlusion from 149 +/- 14 mL/min during control conditions to 111 +/- 15 mL/min (P < .05), decreased the duration of reactive hyperemia from 49 +/- 6 to 33 +/- 3 seconds (P < .05), and decreased reactive hyperemia excess flow from 33 +/- 5 to 20 +/- 4 mL (P < .05).

CONCLUSIONS

These data demonstrate that K+ATP channels modulate coronary vasomotor tone under resting conditions and contribute to coronary vasodilation during ischemia. However, the coronary vasculature retains the capacity to dilate in response to increases in oxygen demand produced by exercise when K+ATP channels are blocked.

摘要

背景

冠状动脉血管张力的代谢调节机制仍不清楚。因此，我们研究了血管平滑肌K⁺ATP通道在静息状态下、跑步机运动引起心肌代谢需求增加时以及对短暂缺血刺激的反应中调节冠状动脉血流的作用。

方法与结果

对10只长期植入仪器的犬在静息状态下以及在对照条件下和冠状动脉内以10和50微克·千克⁻¹·分钟⁻¹的速率输注K⁺ATP通道阻滞剂格列本脲期间进行四阶段运动方案时进行了研究。格列本脲（50微克·千克⁻¹·分钟⁻¹）使静息时冠状动脉血流从51±4降至42±6毫升/分钟（P<.05），使心肌耗氧量从5.70±0.31降至4.11±0.56毫升O₂/分钟（P<.05），并使收缩期室壁增厚从21±3%降至12±3%（P<.05）。当冠状动脉血流通过冠状动脉内硝普钠恢复到对照水平时，格列本脲引起的收缩期室壁增厚的抑制作用被逆转，这表明格列本脲在静息状态下对冠状动脉血流有主要作用。然而，格列本脲并未损害运动期间发生的冠状动脉血流、心肌耗氧量和收缩期室壁增厚的增加。在8只清醒静息的犬中，50微克·千克⁻¹·分钟⁻¹的格列本脲使20秒冠状动脉闭塞后的峰值反应性充血血流速率从对照条件下的149±14毫升/分钟降至111±15毫升/分钟（P<.05），使反应性充血持续时间从49±6秒降至33±3秒（P<.05），并使反应性充血过量血流从3±5毫升降至20±4毫升（P<.05）。