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

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; 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.

• Authors: Pasquale Pagliaro, Daniele Mancardi, Raffaella Rastaldo, Claudia Penna, Donatella Gattullo, Katrina M Miranda, Martin Feelisch, David A Wink, David A Kass, Nazareno Paolocci
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 34 Issue 1 Pg. 33-43 (Jan 01 2003) ISSN: 0891-5849 [Print] United States
• PMID: 12498977 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Nitrogen Oxides
• Sulfhydryl Compounds
• nitroxyl

Topics

• Animals
• Ischemic Preconditioning, Myocardial
• Male
• Myocardial Reperfusion Injury (metabolism)
• Nitrogen Oxides (metabolism)
• Rats
• Rats, Wistar
• Sulfhydryl Compounds (metabolism)