Enzyme independent formation of nitric oxide is triggered during myocardial ischemia and results in post-ischemic injury

Jay L. Zweier, Penghai Wang, Alexandre Samouilov, Periannan Kuppusamv

Research output: Contribution to journalArticle

Abstract

We have recently shown that nitric oxide, NO, generation is greatly increased in ischémie tissues and results in cellular injury. While it has been generally assumed that NO formation in biological tissues is solely due to direct synthesis by specific nitric oxide synthase enzymes (NOS), we observe that in ischémie tissues large quantities of NO can be formed by a mechanism which is not enzyme dependent. Electron paramagnetic resonance, EPR, spectroscopy was applied to directly measure NO generation in the ischémie heart. NO bound to either intriasic heme proteins or to (he spin trap Fe-MGD gives rise to characteristic triplet signals which enable definitive measurement of NO formed within the heart. While only trace NO triplet signals were seen prior to ischemia, during ischemia these signals greatly increased indicating that marked NO generation occurred. While with short ischémie durations of 30 min or less, inhibition of NOS decreased NO formation, inhibition was incomplete and with increasing durations of ischemia less that 50% inhibition was seen. When hearts were labeled with 1SN nitrite and then subjected to ischemia prominent doublet signals were observed arising from the I5N coupling to the unpaired electron, demonstrating that during ischemia nitrite was directly reduced to NO. With long periods of ischemia progressing to necrosis this mechanism of NO formation predominated and resulted in myocardial injury with a loss of contractile function. The existence of this enzyme independent mechanism of NO formation has important implications in the pathogenesis and treatment of tissue injury.

Original languageEnglish (US)
JournalFASEB Journal
Volume10
Issue number3
StatePublished - 1996

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

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