Document Detail


Postischemic recovery and oxidative stress are independent of nitric-oxide synthases modulation in isolated rat heart.
MedLine Citation:
PMID:  12235245     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
During myocardial ischemia and reperfusion, nitric oxide ((.)NO) was shown to exert either beneficial or detrimental effects. Uncoupled (.)NO synthases (NOS) can generate superoxide anion under suboptimal concentrations of substrate and cofactors. The aim of our study was to investigate the role of NOS modulation on 1) the evolution of functional parameters and 2) the amount of free radicals released during an ischemia-reperfusion sequence. Isolated perfused rat hearts underwent 30 min of total ischemia, followed by 30 min of reperfusion in the presence of N(G)-nitro-D- or L-arginine methyl ester (NAME, 100 microM) or of D- or L-arginine (3 mM). Functional parameters were recorded and coronary effluents were analyzed with electron spin resonance to identify and quantify the amount of alpha-phenyl-N-tert-butylnitrone spin adducts produced during reperfusion. The antioxidant capacities of the compounds were determined with the oxygen radical absorbance capacity test. L-NAME-treated hearts showed a reduction of coronary flow and contractile performance, although neither L-NAME nor L-arginine improved the recovery of coronary flow, left end diastolic ventricular pressure, rate pressure product, and duration of reperfusion arrhythmia, compared with their D-specific enantiomers. A large and long-lasting release of alkyl/alkoxyl radicals was detected upon reperfusion, but no differences of free radical release were observed between D- and L-NAME or D- and L-arginine treatment. These results may indicate that, in our experimental conditions, cardiac NOS might not be a major factor implicated in the oxidative burst that follows a global myocardial ischemia.
Authors:
Catherine Vergely; Caroline Perrin-Sarrado; Gaëlle Clermont; Luc Rochette
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  303     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  2002 Oct 
Date Detail:
Created Date:  2002-09-17     Completed Date:  2002-10-21     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  149-57     Citation Subset:  IM    
Affiliation:
Laboratoire de Physiopathologie et Pharmacologie Cardiovasculaires Expérimentales, Facultés de Médecine et Pharamacie, Dijon, France. catherine.vergely@u-bourgogne.fr
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MeSH Terms
Descriptor/Qualifier:
Animals
Arginine / pharmacology
Blood Pressure / drug effects,  physiology
Coronary Circulation / drug effects,  physiology
Heart / drug effects,  physiology,  physiopathology*
Heart Rate / drug effects,  physiology
Kinetics
Myocardial Ischemia / physiopathology*
Myocardial Reperfusion
Myocardium / enzymology*
NG-Nitroarginine Methyl Ester / pharmacology
Nitric Oxide Synthase / metabolism*
Oxidative Stress / physiology*
Perfusion / methods
Rats
Superoxides / metabolism
Ventricular Function, Left / drug effects,  physiology
Chemical
Reg. No./Substance:
11062-77-4/Superoxides; 50903-99-6/NG-Nitroarginine Methyl Ester; 74-79-3/Arginine; EC 1.14.13.39/Nitric Oxide Synthase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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