Glibenclamide, a specific inhibitor of ATP-sensitive K+ channels, inhibits coronary vasodilation induced by angiotensin II-receptor antagonists

J Cardiovasc Pharmacol. 1997 Sep;30(3):313-9. doi: 10.1097/00005344-199709000-00007.

Abstract

The purpose of our study was test the hypothesis that endogenous angiotensin II contributes to the basal coronary artery tone by acting at vascular ATP-sensitive K+ (K+ATP) channels. Coronary blood flow (CBF) and other hemodynamic parameters were measured in anesthetized dogs. Intracoronary infusion of the selective antagonists of angiotensin II AT1 receptors (L-158,809 and E4177) increased CHF without affecting other hemodynamic parameters, indicating that endogenous angiotensin II caused coronary vaso-constriction through the AT1 subtype receptors. Coronary vasodilation in response to AT1 receptor antagonists was blunted by pretreatment with glibenclamide (a specific inhibitor of K+ATP channels; p < 0.01) but not by either an adenosine-receptor antagonist or an inhibitor of nitric oxide synthesis. Coronary vasodilation in response to AT1-receptor antagonists was partly reduced (p < 0.01) by PD-123319 (the AT2-receptor antagonist). Glibenclamide had no effect on coronary vasodilation induced by sodium nitroprusside. These results indicate that in dogs in vivo, coronary vasodilation in response to AT 1-receptor antagonists inhibited markedly by glibenclamide and partly by PD-123319, suggesting that endogenous angiotensin II contributes to the maintenance of basal coronary vascular tone by acting at K+ATP channels through its receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin Receptor Antagonists*
  • Animals
  • Antihypertensive Agents / antagonists & inhibitors
  • Antihypertensive Agents / pharmacology
  • Coronary Circulation / drug effects
  • Coronary Vessels / drug effects*
  • Dogs
  • Enzyme Inhibitors / pharmacology
  • Glyburide / pharmacology*
  • Hypoglycemic Agents / pharmacology*
  • Imidazoles / antagonists & inhibitors
  • Imidazoles / pharmacology
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Potassium Channel Blockers*
  • Pyridines / pharmacology
  • Tetrazoles / antagonists & inhibitors
  • Tetrazoles / pharmacology
  • Vasodilation / drug effects*

Substances

  • Angiotensin Receptor Antagonists
  • Antihypertensive Agents
  • Enzyme Inhibitors
  • Hypoglycemic Agents
  • Imidazoles
  • Potassium Channel Blockers
  • Pyridines
  • Tetrazoles
  • PD 123319
  • L 158809
  • Glyburide
  • NG-Nitroarginine Methyl Ester