Nitroxyl affords thiol-sensitive myocardial protective effects akin to early preconditioning

Pasquale Pagliaro, Daniele Mancardi, Raffaella Rastaldo, Claudia Penna, Donatella Gattullo, Katrina M. Miranda, Martin Feelisch, David A. Wink, David A. Kass, Nazareno Paolocci

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166 Scopus citations

Abstract

Nitric oxide (NO) donors mimic the early phase of ischemic preconditioning (IPC). The effects of nitroxyl (HNO/NO-), the one-electron reduction product of NO, on ischemia/reperfusion (I/R) injury are unknown. Here we investigated whether HNO/NO-, produced by decomposition of Angeli's salt (AS; Na2N2O3), has a cardioprotective effect in isolated perfused rat hearts. Effects were examined after intracoronary perfusion (19 min) of either AS (1 μM), the NO donor diethylamine/NO (DEA/NO, 0.5 μM), vehicle (100 nM NaOH) or buffer, followed by global ischemia (30 min) and reperfusion (30 min or 120 min in a subset of hearts). IPC was induced by three cycles of 3 min ischemia followed by 10 min reperfusion prior to I/R. The extent of I/R injury under each intervention was assessed by changes in myocardial contractility as well as lactate dehydrogenase (LDH) release and infarct size. Postischemic contractility, as indexed by developed pressure and dP/dtmax, was similarly improved with IPC and pre-exposure to AS, as opposed to control or DEA/NO-treated hearts. Infarct size and LDH release were also significantly reduced in IPC and AS groups, whereas DEA/NO was less effective in limiting necrosis. Co-infusion in the triggering phase of AS and the nitroxyl scavenger, N-acetyl-L-cysteine (4 mM) completely reversed the beneficial effects of AS, both at 30 and 120 min reperfusion. Our data show that HNO/NO- affords myocardial protection to a degree similar to IPC and greater than NO, suggesting that reactive nitrogen oxide species are not only necessary but also sufficient to trigger myocardial protection against reperfusion through species-dependent, pro-oxidative, and/or nitrosative stress-related mechanisms.

Original languageEnglish (US)
Pages (from-to)33-43
Number of pages11
JournalFree Radical Biology and Medicine
Volume34
Issue number1
DOIs
StatePublished - Jan 1 2003
Externally publishedYes

Keywords

  • Angeli's salt
  • Diethylamine/NO complex
  • Free radicals
  • Ischemia/reperfusion
  • Myocardial necrosis
  • N-acetyl-L-cysteine
  • Nitric oxide
  • Nitroxyl
  • Preconditioning

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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    Pagliaro, P., Mancardi, D., Rastaldo, R., Penna, C., Gattullo, D., Miranda, K. M., Feelisch, M., Wink, D. A., Kass, D. A., & Paolocci, N. (2003). Nitroxyl affords thiol-sensitive myocardial protective effects akin to early preconditioning. Free Radical Biology and Medicine, 34(1), 33-43. https://doi.org/10.1016/S0891-5849(02)01179-6