Document Detail

NO and PGI(2) in coronary endothelial dysfunction in transgenic mice with dilated cardiomyopathy.
MedLine Citation:
PMID:  18431525     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: The aim of the present work was to analyze coronary endothelial function in the transgenic mouse model of dilated cardiomyopathy (Tgalphaq*44 mice). METHODS: Coronary vasodilatation, both NO-dependent (induced by bradykinin) and PGI(2)-dependent (induced by acetylcholine), was assessed in the isolated hearts of Tgalphaq*44 and FVB mice. Cardiac function was analyzed in vivo (MRI). RESULTS: In Tgalphaq*44 mice at the age of 2-4 months cardiac function was preserved and there were no alterations in endothelial function. By contrast, in Tgalphaq*44 mice at the age of 14-16 months cardiac function was significantly impaired and NO, but not PGI(2)-dependent coronary function was altered. Interestingly, the basal level of PGI(2) in coronary circulation increased fourfold as compared to FVB mice. Cardiac O(2) (-) production increased 1.5-fold and 3-fold in Tgalphaq*44 vs. FVB mice at the age of 2-6 and 14-16 months, respectively, and was inhibited by apocynin. Interestingly, inhibition of NADPH oxidase or NOS-3 normalized augmented PGI(2) production in Tgalphaq*44 mice. There was also an increased expression of gp91phox in Tgalphaq*44 vs. FVB hearts, without evident alterations in the expression of COX-1, COX-2, NOS-3 and PGI(2)-synthase. CONCLUSIONS: In the mouse model of dilated cardiomyopathy, endothelial dysfunction in coronary circulation is present in the late but not the early stage of heart failure pathology and is characterized by a decrease in NO bioavailability and a compensatory increase in PGI(2). Both the decrease in NO activity and the increase in PGI(2) activity may result from excessive O(2) (-) production by cardiac NADPH oxidase in Tgalphaq*44 hearts.
Lukasz Drelicharz; Valery Kozlovski; Tomasz Skorka; Sylwia Heinze-Paluchowska; Andrzej Jasinski; Anna Gebska; Tomasz Guzik; Rafal Olszanecki; Leszek Wojnar; Ulrike Mende; Gabor Csanyi; Stefan Chlopicki
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-04-22
Journal Detail:
Title:  Basic research in cardiology     Volume:  103     ISSN:  0300-8428     ISO Abbreviation:  Basic Res. Cardiol.     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-08-21     Completed Date:  2008-11-14     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0360342     Medline TA:  Basic Res Cardiol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  417-30     Citation Subset:  IM    
Dept. of Experimental Pharmacology, Jagiellonian University Medical College, Grzegorzecka 16, Krakow, 31-531, Poland.
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MeSH Terms
6-Ketoprostaglandin F1 alpha / metabolism
Age Factors
Cardiomyopathy, Dilated / metabolism*
Coronary Artery Disease / metabolism*
Cyclooxygenase 1 / metabolism
Cyclooxygenase 2 / metabolism
Cytochrome P-450 Enzyme System / metabolism
Disease Models, Animal
Endothelium, Vascular / metabolism*
Epoprostenol / metabolism*
Heart Failure / metabolism
Intramolecular Oxidoreductases / metabolism
Membrane Proteins / metabolism
Mice, Inbred Strains
Mice, Transgenic
Myocardium / metabolism
NADPH Oxidase / metabolism
Nitric Oxide / metabolism*
Nitric Oxide Synthase Type II / metabolism
Nitric Oxide Synthase Type III
Superoxides / metabolism
Vasodilation / physiology
Reg. No./Substance:
0/Membrane Proteins; 10102-43-9/Nitric Oxide; 11062-77-4/Superoxides; 35121-78-9/Epoprostenol; 58962-34-8/6-Ketoprostaglandin F1 alpha; 9035-51-2/Cytochrome P-450 Enzyme System; EC Oxide Synthase Type II; EC Oxide Synthase Type III; EC protein, mouse; EC 1.14.99.-/Ptgs2 protein, mouse; EC 1; EC 2; EC protein, mouse; EC Oxidase; EC 5.3.-/Intramolecular Oxidoreductases; EC synthetase

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