Resveratrol attenuates acute hypoxic injury in cardiomyocytes: correlation with inhibition of iNOS-NO signaling pathway

Eur J Pharm Sci. 2011 Oct 9;44(3):416-21. doi: 10.1016/j.ejps.2011.08.029. Epub 2011 Sep 5.

Abstract

Aim: To investigate the effect of resveratrol on hypoxia-induced cardiomyocytes injury and its potential mechanism.

Methods: Cell injury was evaluated by supernatant lactate dehydrogenase (LDH) assay and cell viability. NO production in cardiomyocytes were assessed by Griess reagent, expressions of inducible nitric oxide synthase (iNOS) and hypoxia-inducible factor 1 (HIF-1α) were determined reverse transcription polymerase chain reaction (RT-PCR). HIF-1α protein was determined by Western blot.

Results: Hypoxia increased LDH release, decreased cell viability. Pretreatment with resveratrol (10, 25, and 50μM) decreased LDH release and increased cell viability. Resveratrol suppressed the mRNA expression of iNOS as well as NO production in hypoxia-induced cardiomyocytes. Consistent with the inhibitory effect on iNOS protein expression, resveratrol inhibited iNOS mRNA expression. Resveratrol also inhibited HIF-1α mRNA expression.

Conclusions: These results suggested that resveratrol attenuates acute hypoxic injury in cardiomyocytes, and the mechanism might be associated with inhibition of iNOS-NO signaling pathway via HIF-1α.

MeSH terms

  • Animals
  • Animals, Newborn
  • Cardiotonic Agents / pharmacology*
  • Cell Culture Techniques
  • Cell Hypoxia / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Culture Media / chemistry
  • Lactate Dehydrogenases / metabolism
  • Male
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / enzymology
  • Myocytes, Cardiac / metabolism
  • Nitric Oxide / antagonists & inhibitors*
  • Nitric Oxide Synthase Type II / antagonists & inhibitors*
  • Rats
  • Rats, Sprague-Dawley
  • Resveratrol
  • Signal Transduction / drug effects*
  • Stilbenes / pharmacology*

Substances

  • Cardiotonic Agents
  • Culture Media
  • Stilbenes
  • Nitric Oxide
  • Lactate Dehydrogenases
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Resveratrol