Nicorandil reduces myocardial no-reflow by protection of endothelial function via the activation of KATP channel

Clin Chim Acta. 2006 Dec;374(1-2):100-5. doi: 10.1016/j.cca.2006.05.039. Epub 2006 Jun 3.

Abstract

Introduction: It has been found that nicorandil can attenuate myocardial no-reflow. However, the exact cause of this beneficial effect has remained unclear. We investigated whether the beneficial effect of nicorandil on myocardial no-reflow could be partly due to its protection against endothelial dysfunction.

Methods: Ligation area and area of no-reflow were determined echocardiographically and pathologically in sixty-two animals randomized into 7 study groups: 9 controls, 9 nicorandil-treated, 8 glibenclamide (K(ATP) channel blocker)-treated, 10 N(G)-monomethyl-L-arginine (L-NMMA, nonselective nitric oxide synthase antagonist)-treated, 10 nicorandil and glibenclamide-treated, 8 nicorandil and L-NMMA-treated and 8 sham-operated. The acute myocardial infarction and reperfusion model was created with one 3-h occlusion of the left anterior descending coronary artery followed by 2 h of reperfusion. Constitutive nitric oxide synthase (cNOS) activity and inducible nitric oxide synthase (iNOS) activity were also quantified.

Results: Compared with the control group, nicorandil significantly improved ventricular function, increased coronary blood flow volume (P<0.01), decreased area of no-reflow and reduced necrosis area. Nicorandil also increased the cNOS activity and decreased iNOS activity (P<0.05). L-NMMA and glibenclamide abrogated the effects of nicorandil on ventricular function, coronary blood flow volume, area of no-reflow, necrosis area and cNOS activity, but not iNOS activity.

Conclusions: The beneficial effect of nicorandil on myocardial no-reflow could be due to its protection of endothelial function via the activation of K(ATP) channel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antihypertensive Agents / pharmacology
  • Coronary Circulation / drug effects*
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiopathology
  • Glyburide / pharmacology
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / physiopathology
  • Nicorandil / pharmacology*
  • Nitric Oxide Synthase / analysis
  • Organ Size / drug effects
  • Potassium Channels / metabolism*
  • Swine
  • Swine, Miniature
  • Up-Regulation

Substances

  • Antihypertensive Agents
  • Potassium Channels
  • mitochondrial K(ATP) channel
  • Nicorandil
  • Nitric Oxide Synthase
  • Glyburide