Pagliaro, Pasquale, Mancardi, Daniele, Rastaldo, Raffaella, Penna, Claudia, Gattullo, Donatella, Miranda, Katrina M., Feelisch, Martin, Wink, David A., Kass, David A. and Paolocci, Nazareno
Nitroxyl affords thiol-sensitive myocardial protective effects akin to early preconditioning
Free Radical Biology and Medicine, 34, (1), . (doi:10.1016/S0891-5849(02)01179-6). (PMID:12498977).
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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.
|Digital Object Identifier (DOI):
||ischemia/reperfusion, preconditioning, myocardial necrosis, nitroxyl, angeli’s salt, nitric oxide, diethylamine/NO complex, N-acetyl-L-cysteine, free radicals
||Clinical & Experimental Sciences
|17 December 2002||e-pub ahead of print|
|1 January 2003||Published|
||22 Jun 2012 11:31
||17 Apr 2017 17:13
|Further Information:||Google Scholar|
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