Affiliation:
1. Department of Medicine, University of Minnesota Medical School, Minneapolis 55455.
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.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine
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