Document Detail


Acute inhibition of myoglobin impairs contractility and energy state of iNOS-overexpressing hearts.
MedLine Citation:
PMID:  12775582     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Elevated cardiac levels of nitric oxide (NO) generated by inducible nitric oxide synthase (iNOS) have been implicated in the development of heart failure. The surprisingly benign phenotype of recently generated mice with cardiac-specific iNOS overexpression (TGiNOS) provided the rationale to investigate whether NO scavenging by oxymyoglobin (MbO2) yielding nitrate and metmyoglobin (metMb) is involved in preservation of myocardial function in TGiNOS mice. 1H nuclear magnetic resonance (NMR) spectroscopy was used to monitor changes of cardiac myoglobin (Mb) metabolism in isolated hearts of wild-type (WT) and TGiNOS mice. NO formation by iNOS resulted in a significant decrease of the MbO2 signal and a concomitantly emerging metMb signal in spectra of TGiNOS hearts only (DeltaMbO2: -46.3+/-38.4 micromol/kg, DeltametMb: +41.4+/-17.6 micromol/kg, n=6; P<0.05) leaving contractility and energetics unaffected. Inhibition of the Mb-mediated NO degradation by carbon monoxide (20%) led to a deterioration of myocardial contractility in TGiNOS hearts (left ventricular developed pressure: 78.2+/-8.2% versus 96.7+/-4.6% of baseline, n=6; P<0.005), which was associated with a profound pertubation of cardiac energy state as assessed by 31P NMR spectroscopy (eg, phosphocreatine: 13.3+/-1.3 mmol/L (TGiNOS) versus 15.9+/-0.7 mmol/L (WT), n=6; P<0.005). These alterations could be fully antagonized by the NOS inhibitor S-ethylisothiourea. Our findings demonstrate that myoglobin serves as an important cytoplasmic buffer of iNOS-derived NO, which determines the functional consequences of iNOS overexpression.
Authors:
Carsten Wunderlich; Ulrich Flögel; Axel Gödecke; Jacqueline Heger; Jürgen Schrader
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2003-05-29
Journal Detail:
Title:  Circulation research     Volume:  92     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2003 Jun 
Date Detail:
Created Date:  2003-06-27     Completed Date:  2003-09-24     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1352-8     Citation Subset:  IM    
Affiliation:
Institute for Cardiovascular Physiology, Heinrich-Heine-University, Düsseldorf, Germany.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / metabolism
Animals
Arginine / pharmacology
Carbon Dioxide / pharmacology
Carbon Monoxide / pharmacology
Enzyme Inhibitors / pharmacology
Genotype
Heart / drug effects,  physiology*
Isothiuronium / analogs & derivatives*,  pharmacology
Magnetic Resonance Spectroscopy / methods
Metmyoglobin / metabolism
Mice
Mice, Transgenic
Myocardial Contraction / drug effects,  physiology
Myocardium / enzymology,  metabolism*
Myoglobin / antagonists & inhibitors,  metabolism*
Nitrates / metabolism
Nitric Oxide Synthase / antagonists & inhibitors,  genetics,  metabolism*
Nitric Oxide Synthase Type II
Nitrites / metabolism
Nitrogen / pharmacology
Oxygen / pharmacology
Perfusion / methods
Phosphocreatine / metabolism
Ventricular Pressure / drug effects
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Myoglobin; 0/Nitrates; 0/Nitrites; 0/carboxymyoglobin; 0/oxymyoglobin; 124-38-9/Carbon Dioxide; 12772-23-5/Metmyoglobin; 22584-04-9/Isothiuronium; 2986-20-1/etiron; 56-65-5/Adenosine Triphosphate; 630-08-0/Carbon Monoxide; 67-07-2/Phosphocreatine; 74-79-3/Arginine; 7727-37-9/Nitrogen; 7782-44-7/Oxygen; 8063-77-2/carbogen; EC 1.14.13.39/Nitric Oxide Synthase; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 1.14.13.39/Nos2 protein, mouse
Comments/Corrections
Comment In:
Circ Res. 2003 Oct 3;93(7):e74   [PMID:  14525922 ]

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