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PMID: 15347817 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Reduction of nitrite to nitric oxide during ischemia protects against myocardial ischemia-reperfusion damage.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 37 ·2004-09-14 ·Pages 13683-8

Webb A, Bond R, McLean P, Uppal R, Benjamin N, Ahluwalia A

Abstract

Nitric oxide (NO.) is thought to protect against the damaging effects of myocardial ischemia-reperfusion injury, whereas xanthine oxidoreductase (XOR) normally causes damage through the generation of reactive oxygen species. In the heart, inorganic nitrite (NO(2)(-)) has the potential to act as an endogenous store of NO., liberated specifically during ischemia. Using a detection method that we developed, we report that under ischemic conditions both rat and human homogenized myocardium and the isolated perfused rat heart (Langendorff preparation) generate NO. from NO(2)(-) in a reaction that depends on XOR activity. Functional studies of rat hearts in the Langendorff apparatus showed that nitrite (10 and 100 microM) reduced infarct size from 47.3 +/- 2.8% (mean percent of control +/- SEM) to 17.9 +/- 4.2% and 17.4 +/- 1.0%, respectively (P < 0.001), and was associated with comparable improvements in recovery of left ventricular function. This protective effect was completely blocked by the NO. scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazole-1-oxyl 3-oxide (carboxy-PTIO). In summary, the generation of NO. from NO(2)(-), by XOR, protects the myocardium from ischemia-reperfusion injury. Hence, if XOR is presented with NO(2)(-) as an alternative substrate, the resultant effects of its activity may be protective, by means of its production of NO. , rather than damaging.

MeSH Terms
Animals Cardiotonic Agents/metabolism Humans Hydrogen-Ion Concentration Male Myocardial Ischemia/enzymology,metabolism Myocardial Reperfusion Injury/enzymology,metabolism,prevention & control Myocardium/enzymology,metabolism Nitric Oxide/metabolism Nitrites/metabolism Oxidation-Reduction Rats Rats, Wistar Xanthine/metabolism Xanthine Oxidase/antagonists & inhibitors,metabolism
Chemicals
Cardiotonic Agents Nitrites Xanthine Nitric Oxide Xanthine Oxidase
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Webb Andrew
Clinical Pharmacology, William Harvey Research Institute, Barts and the London, Queen Mary's School of Medicine and Dentistry, Charterhouse Square, London EC1M 6BQ, England.
Bond Richard
McLean Peter
Uppal Rakesh
Benjamin Nigel
Ahluwalia Amrita
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0402927101
Published
2004-09-14
Epub
2004-00-03
Pages
13683-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC518813
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.0402927101 PMC Full Text View journal details
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