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

Research output: Contribution to journalArticle

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

Fingerprint

Sulfhydryl Compounds
Nitric Oxide
Ischemic Preconditioning
Reperfusion
Nitric Oxide Donors
Reperfusion Injury
L-Lactate Dehydrogenase
Ischemia
nitroxyl
Reactive Nitrogen Species
Acetylcysteine
Rats
Buffers
Necrosis
Perfusion
Electrons
Decomposition
Pressure

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

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

Cite this

Nitroxyl affords thiol-sensitive myocardial protective effects akin to early preconditioning. / Pagliaro, Pasquale; Mancardi, Daniele; Rastaldo, Raffaella; Penna, Claudia; Gattullo, Donatella; Miranda, Katrina M.; Feelisch, Martin; Wink, David A.; Kass, David A; Paolocci, Nazareno.

In: Free Radical Biology and Medicine, Vol. 34, No. 1, 01.01.2003, p. 33-43.

Research output: Contribution to journalArticle

Pagliaro, P, Mancardi, D, Rastaldo, R, Penna, C, Gattullo, D, Miranda, KM, Feelisch, M, Wink, DA, Kass, DA & Paolocci, N 2003, 'Nitroxyl affords thiol-sensitive myocardial protective effects akin to early preconditioning', Free Radical Biology and Medicine, vol. 34, no. 1, pp. 33-43. https://doi.org/10.1016/S0891-5849(02)01179-6
Pagliaro, Pasquale ; Mancardi, Daniele ; Rastaldo, Raffaella ; Penna, Claudia ; Gattullo, Donatella ; Miranda, Katrina M. ; Feelisch, Martin ; Wink, David A. ; Kass, David A ; Paolocci, Nazareno. / Nitroxyl affords thiol-sensitive myocardial protective effects akin to early preconditioning. In: Free Radical Biology and Medicine. 2003 ; Vol. 34, No. 1. pp. 33-43.
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AU - Gattullo, Donatella

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N2 - 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.

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