| Formation of hydrogen peroxide and reduction of peroxynitrite via dismutation of superoxide at reperfusion enhances myocardial blood flow and oxygen consumption in postischemic mouse heart. | |
| | |
MedLine Citation:
|
PMID: 18685120 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Reactive oxygen/nitrogen species suppress myocardial oxygen consumption. In this study, we determined that endogenous hydrogen peroxide through dismutation of superoxide enhances postischemic myocardial blood perfusion and oxygen consumption. Electron paramagnetic resonance oximetry was applied to monitor in vivo tissue Po2 in mouse heart subjected to regional ischemia reperfusion. Heart rate, arterial blood pressure, blood flow, infarction, and activities of mitochondrial NADH dehydrogenase and cytochrome c oxidase were measured in six groups of wild-type (WT) and endothelial nitricoxide synthase knock-out (eNOS(-/-)) mice treated with phosphate-buffered saline (PBS), superoxide dismutase mimetic (SOD(m)) M40403 [a manganese(II)-bis(cyclohexylpyridine)-substituted macrocyclic superoxide dismutase mimetic, C21H35Cl2MnN5], 10006329 EUK 134 [EUK134, manganese 3-methoxy N,N(1)-bis(salicyclidene)ethylenediamine chloride], and SOD(m) plus glibenclamide to study the protective effect of hydrogen peroxide via dismutation of superoxide on the activation of sarcolemmal potassium channels. In the PBS group, there was an overshoot of tissue Po2 after reperfusion. Treatment with SOD(m), EUK134, and SOD(m) + glibenclamide protected mitochondrial enzyme activities, reduced infarct size, and suppressed the postischemic hyperoxygenation. In particular, in the SOD(m)-treated group, there was a transient peak of tissue Po2 at 9 min after reperfusion, which was dependent on endogenous hydrogen peroxide but not nitric oxide formation as it appeared in both WT and eNOS(-/-) mice. Blood flow and rate pressure product were higher in the SOD(m) group than in other groups, which contributed to the transient oxygen peak. Thus, SOD mimetics protected mouse heart from superoxide-induced reperfusion injury. With treatment of different SOD mimetics, it is concluded that endogenous hydrogen peroxide via dismutation of superoxide at reperfusion enhances postischemic myocardial blood perfusion and mitochondrial oxygen consumption, possibly through activation of sarcolemmal ATP-sensitive potassium channels. |
| | |
Authors:
|
Yi Xu; Bin Liu; Jay L Zweier; Guanglong He |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2008-08-06 |
Journal Detail:
|
Title: The Journal of pharmacology and experimental therapeutics Volume: 327 ISSN: 1521-0103 ISO Abbreviation: J. Pharmacol. Exp. Ther. Publication Date: 2008 Nov |
Date Detail:
|
Created Date: 2008-10-20 Completed Date: 2008-11-13 Revised Date: 2011-08-01 |
Medline Journal Info:
|
Nlm Unique ID: 0376362 Medline TA: J Pharmacol Exp Ther Country: United States |
Other Details:
|
Languages: eng Pagination: 402-10 Citation Subset: IM |
Affiliation:
|
The Center for Biomedical EPR Spectroscopy and Imaging, Davis Heart and Lung Research Institute, and Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University College of Medicine, Columbus, Ohio, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Coronary Circulation* Electron Spin Resonance Spectroscopy Glyburide / pharmacology Hemodynamics / drug effects Hydrogen Peroxide / metabolism* KATP Channels / physiology Male Mice Mice, Inbred C57BL Myocardial Ischemia / metabolism* Myocardial Reperfusion Myocardium / metabolism* Nitric Oxide / metabolism Nitric Oxide Synthase Type II / physiology Nitric Oxide Synthase Type III Organometallic Compounds / pharmacology Oximetry Oxygen Consumption* Peroxynitrous Acid / metabolism* Salicylates / pharmacology Superoxide Dismutase / physiology* |
| Grant Support | |
ID/Acronym/Agency:
|
HL-081630/HL/NHLBI NIH HHS; R01 HL038324-19/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/EUK-134; 0/KATP Channels; 0/Organometallic Compounds; 0/Salicylates; 10102-43-9/Nitric Oxide; 10238-21-8/Glyburide; 14691-52-2/Peroxynitrous Acid; 7722-84-1/Hydrogen Peroxide; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 1.14.13.39/Nos3 protein, mouse; EC 1.15.1.1/Superoxide Dismutase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Approach to the human immunodeficiency virus-infected patient with lipodystrophy.
Next Document: Low copy number and low oxidative damage of mitochondrial DNA are associated with tumor progression ...