Abstract |
The role of neuronal nitric oxide synthase (nNOS) in cardiac ischemia-reperfusion (IR) and ischemia preconditioning (IP) is still controversial. Here, we focused on the possible roles of nNOS in cardiac IR and IP. Wild type C57BL/6 (WT) mice were subjected to coronary artery occlusion for 30 min followed by 24-h reperfusion (IR). Cardiac injury ( infarct size and apoptotic cell number) was increased, associated with elevation of oxidative stress (lipid peroxidation) and nitrative stress ( nitrotyrosine formation). A potent nNOS inhibitor, L-VNIO, and a superoxide dismutase mimetic and peroxynitrite scavenger, MnTBAP, significantly reduced IR-induced increases of oxidative/nitrative stress and cardiac injury. IR-induced cardiac injury in nNOS(-/-) (KO) mice was significantly lower than that in WT mice. MnTBAP markedly reduced IR-induced cardiac injury by suppression of oxidative/nitrative stress in KO mice. Cardiac IP was performed by three cycles of 5-min IR before 30-min ischemia followed by 24-h reperfusion. IP attenuated IR-induced cardiac injury in WT mice associated with reductions of oxidative/nitrative stress. IP-induced reduction of cardiac injury and oxidative/nitrative stress were eliminated by pretreatment with L-VNIO. In contrast with WT mice, IP had no protective effects in nNOS KO mice. In conclusion, nNOS played a dual role during cardiac IR and IP; nNOS exacerbated IR-induced injury by increasing oxidative/nitrative stress and contributed to IP-induced protection by inhibition of oxidative/nitrative stress.
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Authors | Xiao-Mei Lu, Guo-Xing Zhang, Yan-Qiu Yu, Shoji Kimura, Akira Nishiyama, Hiroko Matsuyoshi, Juichiro Shimizu, Miyako Takaki |
Journal | The journal of physiological sciences : JPS
(J Physiol Sci)
Vol. 59
Issue 4
Pg. 253-62
(Jul 2009)
ISSN: 1880-6562 [Electronic] Japan |
PMID | 19340535
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Enzyme Inhibitors
- Free Radical Scavengers
- Metalloporphyrins
- N(5)-(1-imino-3-butenyl)ornithine
- Reactive Nitrogen Species
- Thiobarbituric Acid Reactive Substances
- manganese(III)-tetrakis(4-benzoic acid)porphyrin
- 3-nitrotyrosine
- Tyrosine
- Ornithine
- Nitric Oxide Synthase Type I
- Nos1 protein, mouse
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Topics |
- Animals
- Apoptosis
(drug effects)
- Enzyme Inhibitors
(pharmacology)
- Free Radical Scavengers
(pharmacology)
- Ischemic Preconditioning, Myocardial
- Lipid Peroxidation
(drug effects)
- Metalloporphyrins
(pharmacology)
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Myocardial Infarction
(metabolism, pathology)
- Myocardial Reperfusion Injury
(enzymology, etiology, pathology, prevention & control)
- Myocardium
(metabolism, pathology)
- Nitric Oxide Synthase Type I
(antagonists & inhibitors, deficiency, genetics, physiology)
- Ornithine
(analogs & derivatives, pharmacology)
- Oxidative Stress
(drug effects)
- Reactive Nitrogen Species
(metabolism)
- Thiobarbituric Acid Reactive Substances
(metabolism)
- Tyrosine
(analogs & derivatives, metabolism)
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