Coronary vascular ATP-sensitive potassium channels are activated to a greater extent in spontaneously hypertensive rats than in Wistar-Kyoto rats

J Hypertens. 1996 Feb;14(2):183-9. doi: 10.1097/00004872-199602000-00006.

Abstract

Objective: To determine whether opening of coronary vascular adenosine 5'-triphosphate (ATP)-sensitive potassium (KATP) channels is involved in the maintenance of resting coronary flow in hypertrophied hearts.

Methods: We examined the effects of glibenclamide, a selective inhibitor of KATP channels, on basal coronary vascular tone in Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). Using a Langendorff system, the hearts from WKY rats and SHRs were isolated and perfused with oxygenated Krebs-Henseleit solution at a constant perfusion pressure of 60 and 100 mmHg respectively.

Results: Basal coronary flow and myocardial oxygen consumption (MV02) were similar in SHRs and WKY rats. The percentage decreases in coronary flow with glibenclamide at graded doses were greater (P < 0.01) in SHRs than in WKY rats (n = 8), whereas the percentage decreases in MV02 with glibenclamide were similar in the two groups. The decreases in coronary flow caused by U46619 (a thromboxane A2-mimetic agent) were similar in SHRs and WKY rats (n = 4). The increase in coronary flow caused by pinacidil (a KATP opener) was greater in SHRs than in WKY rats; glibenclamide prevented the pinacidil-induced increase in coronary flow in both SHRs and WKY rats. There was a significant positive correlation between the glibenclamide-induced decrease in coronary flow and the degree of left ventricular hypertrophy (r = 0.54, P < 0.05).

Conclusion: Our results suggest that the basal opening state of coronary vascular KATP channels is activated to a greater extent in SHRs than WKY rats, which may contribute to the maintenance of basal myocardial perfusion in hypertrophied hearts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
  • Adenosine Triphosphate / pharmacology*
  • Animals
  • Coronary Circulation / drug effects
  • Coronary Circulation / physiology
  • Coronary Vessels / drug effects
  • Coronary Vessels / metabolism*
  • Coronary Vessels / physiopathology
  • Glyburide / pharmacology
  • Guanidines / pharmacology
  • Hypertension / metabolism*
  • Hypertension / physiopathology
  • Hypertrophy, Left Ventricular / metabolism
  • Hypertrophy, Left Ventricular / physiopathology
  • Male
  • Myocardium / metabolism
  • Organ Size
  • Oxygen Consumption
  • Pinacidil
  • Potassium Channel Blockers
  • Potassium Channels / drug effects
  • Potassium Channels / metabolism*
  • Prostaglandin Endoperoxides, Synthetic / pharmacology
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Thromboxane A2 / analogs & derivatives
  • Thromboxane A2 / pharmacology
  • Vasoconstrictor Agents / pharmacology
  • Vasodilator Agents / pharmacology

Substances

  • Guanidines
  • Potassium Channel Blockers
  • Potassium Channels
  • Prostaglandin Endoperoxides, Synthetic
  • Vasoconstrictor Agents
  • Vasodilator Agents
  • Thromboxane A2
  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
  • Pinacidil
  • Adenosine Triphosphate
  • Glyburide