Nitric oxide during ischemia attenuates oxidant stress and cell death during ischemia and reperfusion in cardiomyocytes

Hirotaro Iwase, Emmanuel Robin, Robert D. Guzy, Paul T. Mungai, Terry L. Vanden Hoek, Navdeep S. Chandel, Jacques Levraut, Paul T. Schumacker*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Nitric oxide (NO) has been implicated as a cardioprotective agent during ischemia/reperfusion (I/R), but the mechanism of protection is unknown. Oxidant stress contributes to cell death in I/R, so we tested whether NO protects by attenuating oxidant stress. Cardiomyocytes and murine embryonic fibroblasts were administered NO (10-1200 nM) during simulated ischemia, and cell death was assessed during reperfusion without NO. In each case, NO abrogated cell death during reperfusion. Cells overexpressing endothelial NO synthase (NOS) exhibited a similar protection, which was abolished by the NOS inhibitor Nω-nitro-l-arginine methyl ester. Protection was not mediated by guanylate cyclase or the mitochondrial KATP channel, as inhibitors of these systems failed to abolish protection. NO did not prevent decreases in mitochondrial potential, but cells protected with NO demonstrated recovery of potential at reperfusion. Measurements using C11-BODIPY reveal that NO attenuates lipid peroxidation during ischemia and reperfusion. Measurements of oxidant stress using the ratiometric redox sensor HSP-FRET demonstrate that NO attenuates protein oxidation during ischemia. These findings reveal that physiological levels of NO during ischemia can attenuate oxidant stress both during ischemia and during reperfusion. This response is associated with a remarkable attenuation of cell death, suggesting that ischemic cell death may be a regulated event.

Original languageEnglish (US)
Pages (from-to)590-599
Number of pages10
JournalFree Radical Biology and Medicine
Volume43
Issue number4
DOIs
StatePublished - Aug 15 2007

Keywords

  • Antioxidants
  • Fluorescence microscopy
  • Free radicals
  • Mitochondria
  • Myocardial ischemia
  • Reactive oxygen species

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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