Nitroxyl affords thiol-sensitive myocardial protective effects akin to early preconditioning
Nitroxyl affords thiol-sensitive myocardial protective effects akin to early preconditioning
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.
ischemia/reperfusion, preconditioning, myocardial necrosis, nitroxyl, angeli’s salt, nitric oxide, diethylamine/NO complex, N-acetyl-L-cysteine, free radicals
33-43
Pagliaro, Pasquale
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Mancardi, Daniele
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Rastaldo, Raffaella
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Penna, Claudia
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Gattullo, Donatella
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Miranda, Katrina M.
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Feelisch, Martin
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Wink, David A.
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Kass, David A.
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Paolocci, Nazareno
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1 January 2003
Pagliaro, Pasquale
124b3870-e4f8-4f28-865d-39d2e3d8afe6
Mancardi, Daniele
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Rastaldo, Raffaella
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Penna, Claudia
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Gattullo, Donatella
dd267d2e-b936-41e0-8315-04b505e86b80
Miranda, Katrina M.
128fa814-eb00-472f-a5e7-5657e59ac9b9
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Wink, David A.
008b5aec-8c2b-4035-8912-fb6fd530413c
Kass, David A.
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Paolocci, Nazareno
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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 and Medicine, 34 (1), .
(doi:10.1016/S0891-5849(02)01179-6).
(PMID:12498977)
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.
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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
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Local EPrints ID: 337860
URI: http://eprints.soton.ac.uk/id/eprint/337860
ISSN: 0891-5849
PURE UUID: e51d4148-9b81-4aef-b86e-8938fac100e3
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Date deposited: 22 Jun 2012 11:31
Last modified: 15 Mar 2024 03:41
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Author:
Pasquale Pagliaro
Author:
Daniele Mancardi
Author:
Raffaella Rastaldo
Author:
Claudia Penna
Author:
Donatella Gattullo
Author:
Katrina M. Miranda
Author:
David A. Wink
Author:
David A. Kass
Author:
Nazareno Paolocci
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