Role of K+ATP channels in coronary vasodilation during exercise

Dirk J. Duncker, Noëmi S. Van Zon, John D. Altman, Todd J. Pavek, Robert J Bache

Research output: Contribution to journalArticlepeer-review

116 Scopus citations

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 glybenclamide at rates of 10 and 50 μg · kg-1 · min-1. Glybenclamide (50 μg · kg-1 · 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 glybenclamide was reversed when coronary blood flow was restored to the control level with intracoronary nitroprusside, indicating a primary effect of glybenclamide on coronary flow during resting conditions. However, glybenclamide 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 μg · kg-1 · min-1 glybenclamide 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.

Original languageEnglish (US)
Pages (from-to)1245-1253
Number of pages9
JournalCirculation
Volume88
Issue number3
DOIs
StatePublished - Sep 1993

Keywords

  • Blood flow
  • Exercise
  • Ischemia
  • Potassium
  • Vasoconstriction

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