title: Opposite effects of nitric oxide and nitroxyl on postischemic myocardial injury.
abstract: Recent experimental evidence suggests that reactive nitrogen oxide species can contribute significantly to postischemic myocardial injury. The aim of the present study was to evaluate the role of two reactive nitrogen oxide species, nitroxyl (NO(-)) and nitric oxide (NO(.)), in myocardial ischemia and reperfusion injury. Rabbits were subjected to 45 min of regional myocardial ischemia followed by 180 min of reperfusion. Vehicle (0.9% NaCl), 1 micromol/kg S-nitrosoglutathione (GSNO) (an NO(.) donor), or 3 micromol/kg Angeli's salt (AS) (a source of NO(-)) were given i.v. 5 min before reperfusion. Treatment with GSNO markedly attenuated reperfusion injury, as evidenced by improved cardiac function, decreased plasma creatine kinase activity, reduced necrotic size, and decreased myocardial myeloperoxidase activity. In contrast, the administration of AS at a hemodynamically equieffective dose not only failed to attenuate but, rather, aggravated reperfusion injury, indicated by an increased left ventricular end diastolic pressure, myocardial creatine kinase release and necrotic size. Decomposed AS was without effect. Co-administration of AS with ferricyanide, a one-electron oxidant that converts NO(-) to NO(.), completely blocked the injurious effects of AS and exerted significant cardioprotective effects similar to those of GSNO. These results demonstrate that, although NO(.) is protective, NO(-) increases the tissue damage that occurs during ischemia/reperfusion and suggest that formation of nitroxyl may contribute to postischemic myocardial injury.
authors.affiliation: Department of Surgery, Thomas Jefferson University, Philadelphia, PA 19107, USA. xin.ma@mail.tju.edu
authors.forename: X L
authors.initials: XL
authors.lastname: Ma
authors.forename: F
authors.initials: F
authors.lastname: Gao
authors.forename: G L
authors.initials: GL
authors.lastname: Liu
authors.forename: B L
authors.initials: BL
authors.lastname: Lopez
authors.forename: T A
authors.initials: TA
authors.lastname: Christopher
authors.forename: J M
authors.initials: JM
authors.lastname: Fukuto
authors.forename: D A
authors.initials: DA
authors.lastname: Wink
authors.forename: M
authors.initials: M
authors.lastname: Feelisch
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004730:Endothelium, Vascular / Q000502:physiology; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000209:etiology*; D009504:Neutrophils / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology*; D009573:Nitrites / Q000494:pharmacology; D009589:Nitrogen Oxides / Q000378:metabolism*; D009603:Nitroso Compounds / Q000494:pharmacology; D010084:Oxidation-Reduction; D011817:Rabbits; D026422:S-Nitrosoglutathione
chemical_list: D009573:Nitrites; D009589:Nitrogen Oxides; D009603:Nitroso Compounds; C021229:oxyhyponitrite; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D005978:Glutathione; C039900:nitroxyl; D000109:Acetylcholine