JPET

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on August 6, 2008; DOI: 10.1124/jpet.108.142372

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jpet.108.142372v1
327/2/402    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Google Scholar
Right arrow Articles by Xu, Y.
Right arrow Articles by He, G.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Xu, Y.
Right arrow Articles by He, G.


Received for publication June 17, 2008.
Revised August 5, 2008.
Accepted for publication August 5, 2008.

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

Yi Xu 1, Bin Liu 1, Jay L. Zweier 1, Guanglong He 1*

1 The Ohio State University

* Address correspondence to: E-mail: guanglong.he{at}osumc.edu

Abstract

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. EPR 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 eNOS-/- mice treated with phosphate buffered saline (PBS), M40403 (SODm), 10006329 EUK 134 (EUK134), and SODm plus glibenclamide to study the protective effect of hydrogen peroxide via dismutation of superoxide on the activation of sarcolemmal potassium channels. In PBS group, there was an overshoot of tissue Po2 after reperfusion. Treatment with SODm, EUK134, and SODm+glibenclamide protected mitochondrial enzyme activities, reduced infarct size, and suppressed the postischemic hyperoxygenation. In the SODm-treated group particularly, 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 SODm 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.


Key words: EPR oximetry, Ischemia and Reperfusion, Oxygen Consumption, Reactive Oxygen/Nitrogen Species, Superoxide Dismutase, Tissue Oxygenation




Home Help [Feedback] [For Subscribers] [Archive] [Search] --
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2008 by the American Society for Pharmacology and Experimental Therapeutics.