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Nitrite confers protection against myocardial infarction: role of xanthine oxidoreductase, NADPH oxidase and K(ATP) channels. J Mol Cell Cardiol 2007 Oct;43(4):437-44

Date

09/04/2007

Pubmed ID

17765919

Pubmed Central ID

PMC2735077

DOI

10.1016/j.yjmcc.2007.07.057

Scopus ID

2-s2.0-34548846129   104 Citations

Abstract

Reduction of nitrite to nitric oxide during ischemia protects the heart against injury from ischemia/reperfusion. However the optimal dose of nitrite and the mechanisms underlying nitrite-induced cardioprotection are not known. We determined the ability of nitrite and nitrate to confer protection against myocardial infarction in two rat models of ischemia/reperfusion injury and the role of xanthine oxidoreductase, NADPH oxidase, nitric oxide synthase and K(ATP) channels in mediating nitrite-induced cardioprotection. In vivo and in vitro rat models of myocardial ischemia/reperfusion injury were used to cause infarction. Hearts (n=6/group) were treated with nitrite or nitrate for 15 min prior to 30 min regional ischemia and 180 min reperfusion. Xanthine oxidoreductase activity was measured after 15 min aerobic perfusion and 30 min ischemia. Nitrite reduced myocardial necrosis and decline in ventricular function following ischemia/reperfusion in the intact and isolated rat heart in a dose- or concentration-dependent manner with an optimal dose of 4 mg/kg in vivo and concentration of 10 microM in vitro. Nitrate had no effect on protection. Reduction in infarction by nitrite was abolished by the inhibition of flavoprotein reductases and the molybdenum site of xanthine oxidoreductase and was associated with an increase in activity of xanthine dehydrogenase and xanthine oxidase during ischemia. Inhibition of nitric oxide synthase had no effect on nitrite-induced cardioprotection. Inhibition of NADPH oxidase and K(ATP) channels abolished nitrite-induced cardioprotection. Nitrite but not nitrate protects against infarction by a mechanism involving xanthine oxidoreductase, NADPH oxidase and K(ATP) channels.

Author List

Baker JE, Su J, Fu X, Hsu A, Gross GJ, Tweddell JS, Hogg N

Authors

John E. Baker PhD Professor in the Surgery department at Medical College of Wisconsin
Neil Hogg PhD Associate Dean, Professor in the Biophysics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Cardiotonic Agents
Dose-Response Relationship, Drug
KATP Channels
Male
Myocardial Infarction
NADPH Oxidases
Nitrates
Nitric Oxide
Nitrites
Rats
Rats, Sprague-Dawley
Time Factors
Xanthine Dehydrogenase
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a