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PMID: 17765919 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Nitrite confers protection against myocardial infarction: role of xanthine oxidoreductase, NADPH oxidase and K(ATP) channels.

Journal of molecular and cellular cardiology ·Vol. 43 ·No. 4 ·2007-10-00 ·Pages 437-44

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

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.

MeSH Terms
Animals Cardiotonic Agents/pharmacology Dose-Response Relationship, Drug KATP Channels/physiology Male Myocardial Infarction/prevention & control NADPH Oxidases/physiology Nitrates/pharmacology Nitric Oxide/physiology Nitrites/pharmacology Rats Rats, Sprague-Dawley Time Factors Xanthine Dehydrogenase/physiology
Chemicals
Cardiotonic Agents KATP Channels Nitrates Nitrites Nitric Oxide Xanthine Dehydrogenase NADPH Oxidases
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Baker John E
Division of Cardiothoracic Surgery, Medical College of Wisconsin, Milwaukee, WI 53226, USA. [email protected]
Su Jidong
Fu Xiangping
Hsu Anna
Gross Garrett J
Tweddell James S
Hogg Neil
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Article Info
Journal
Journal of molecular and cellular cardiology
Abbr.
J Mol Cell Cardiol
ISSN
0022-2828
DOI
10.1016/j.yjmcc.2007.07.057
Email
[email protected]
Published
2007-10-00
Epub
2007-00-31
Pages
437-44
Language
English
Region
England
NLM ID
0262322
PMCID
PMC2735077
Subset
IM
Grants
NHLBI NIH HHS · HL08361 · United States
NIGMS NIH HHS · R01 GM055792 · United States
NHLBI NIH HHS · R01 HL054075 · United States
NHLBI NIH HHS · R01 HL054075-10 · United States
NIGMS NIH HHS · R29 GM055792 · United States
NIGMS NIH HHS · GM55792 · United States
NHLBI NIH HHS · HL54075 · United States
External Links
PubMed source DOI: 10.1016/j.yjmcc.2007.07.057 PMC Full Text View journal details
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