Blockade of the ATP-sensitive potassium channel modulates reactive hyperemia in the canine coronary circulation

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Abstract

The mechanism of reactive hyperemia remains unknown. We hypothesized that reactive hyperemia was related to the opening of ATP-sensitive potassium channels during coronary occlusion. The resulting hyperpolarization of the smooth muscle cell plasma membrane might reduce calcium influx through voltage-dependent calcium channels and result in relaxation of smooth muscle tone and vasodilation. In eight open-chest, anesthetized dogs, 30-second coronary occlusions resulted in an average flow debt repayment of 200 ± 41%. After low-dose (0.8 μmol/min) and high-dose (3.7 μmol/min) infusion of intracoronary glibenclamide, flow debt repayment fell to 76 ± 14% and 50 ± 8%, respectively (p <0.05 compared with control for both). The decline in flow debt repayment was due to a signficant reduction both in maximum coronary conductance during reactive hyperemia and in its duration. In addition, there was a significant decline in the sensitivity of the coronary circulation to adenosine-induced vasodilation after glibenclamide. While more variable, there was no overall change in the sensitivity of the coronary vasculature to acetylcholine-induced vasodilation after glibenclamide. We conclude that reactive hyperemia is determined in a large part by the ATP-sensitive potassium channel, probably through its effect on membrane potential and voltage-sensitive calcium channels. Because reactive hyperemia was never fully abolished at the highest doses of glibenclamide tested, it is possible that additional mechanisms are involved in the genesis of this complex phenomenon.

Original languageEnglish (US)
Pages (from-to)618-622
Number of pages5
JournalCirculation Research
Volume69
Issue number3
Publication statusPublished - 1991

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Keywords

  • ATP-sensitive potassium channels
  • Coronary blood flow
  • Reactive hyperemia
  • Voltage-dependent calcium channels

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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