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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. and Paolocci, Nazareno (2003) Nitroxyl affords thiol-sensitive myocardial protective effects akin to early preconditioning Free Radical Biology & Medicine, 34, (1), pp. 33-43. (doi:10.1016/S0891-5849(02)01179-6). (PMID:12498977).

Record type: Article


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; Na(2)N(2)O(3)), has a cardioprotective effect in isolated perfused rat hearts. Effects were examined after intracoronary perfusion (19 min) of either AS (1 microM), the NO donor diethylamine/NO (DEA/NO, 0.5 microM), 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/dt(max), 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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e-pub ahead of print date: 17 December 2002
Published date: 1 January 2003
Keywords: ischemia/reperfusion, preconditioning, myocardial necrosis, nitroxyl, angeli’s salt, nitric oxide, diethylamine/NO complex, N-acetyl-L-cysteine, free radicals
Organisations: Clinical & Experimental Sciences


Local EPrints ID: 337860
ISSN: 0891-5849
PURE UUID: e51d4148-9b81-4aef-b86e-8938fac100e3
ORCID for Martin Feelisch: ORCID iD

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Date deposited: 22 Jun 2012 11:31
Last modified: 18 Jul 2017 06:00

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

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