Document Detail

Myoglobin: A scavenger of bioactive NO.
MedLine Citation:
PMID:  11136228     Owner:  NLM     Status:  MEDLINE    
The present study explored the role of myoglobin (Mb) in cardiac NO homeostasis and its functional relevance by employing isolated hearts of wild-type (WT) and myoglobin knockout mice. (1)H NMR spectroscopy was used to measure directly the conversion of oxygenated Mb (MbO(2)) to metmyoglobin (metMb) by reaction with NO. NO was applied intracoronarily (5 nM to 25 microM), or its endogenous production was stimulated with bradykinin (Bk; 10 nM to 2 microM). We found that infusion of authentic NO solutions dose-dependently (>/= 2.5 microM NO) increased metMb formation in WT hearts that was rapidly reversible on cessation of NO infusion. Likewise, Bk-induced release of NO was associated with significant metMb formation in the WT (>/=1 microM Bk). Hearts lacking Mb reacted more sensitively to infused NO in that vasodilatation and the cardiodepressant actions of NO were more pronounced. Similar results were obtained with Bk. The lower sensitivity of WT hearts to changes in NO concentration fits well with the hypothesis that in the presence of Mb, a continuous degradation of NO takes place by reaction of MbO(2) + NO to metMb + NO(3)(-), thereby effectively reducing cytosolic NO concentration. This breakdown protects myocytic cytochromes against transient rises in cytosolic NO. Regeneration of metMb by metMb reductase to Mb and subsequent association with O(2) leads to reformation of MbO(2) available for another NO degradation cycle. Our data indicate that this cycle is crucial in the breakdown of NO and substantially determines the dose-response curve of the NO effects on coronary blood flow and cardiac contractility.
U Flögel; M W Merx; A Godecke; U K Decking; J Schrader
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2001-01-02
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  98     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2001 Jan 
Date Detail:
Created Date:  2001-03-14     Completed Date:  2001-04-26     Revised Date:  2013-06-11    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  735-40     Citation Subset:  IM    
Institute for Cardiovascular Physiology, Heinrich-Heine-University, 40225 Düsseldorf, Germany.
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MeSH Terms
Bradykinin / pharmacology
Coronary Circulation / drug effects
Cytosol / metabolism
Dose-Response Relationship, Drug
Enzyme Inhibitors / pharmacology
Heart / drug effects
Isothiuronium / analogs & derivatives*,  pharmacology
Magnetic Resonance Spectroscopy
Metmyoglobin / biosynthesis
Mice, Knockout
Mitochondria, Heart / drug effects,  metabolism
Models, Biological
Myocardial Contraction / drug effects
Myocardium / metabolism
Myoglobin / genetics,  metabolism*
Nitrates / metabolism
Nitric Oxide / metabolism*,  pharmacology
Nitric Oxide Synthase / antagonists & inhibitors
Vasodilation / drug effects
Vasodilator Agents / pharmacology
omega-N-Methylarginine / pharmacology
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Myoglobin; 0/Nitrates; 0/Vasodilator Agents; 10102-43-9/Nitric Oxide; 12772-23-5/Metmyoglobin; 17035-90-4/omega-N-Methylarginine; 22584-04-9/Isothiuronium; 2986-20-1/etiron; 58-82-2/Bradykinin; EC Oxide Synthase
Erratum In:
Proc Natl Acad Sci U S A 2001 Mar 27;98(7):4276

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