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01-09-2008 | ORIGINAL CONTRIBUTION

NO and PGI₂ in coronary endothelial dysfunction in transgenic mice with dilated cardiomyopathy

Authors: 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

Published in: Basic Research in Cardiology | Issue 5/2008

Abstract

Objective

The aim of the present work was to analyze coronary endothelial function in the transgenic mouse model of dilated cardiomyopathy (Tgαq*44 mice).

Methods

Coronary vasodilatation, both NO-dependent (induced by bradykinin) and PGI₂-dependent (induced by acetylcholine), was assessed in the isolated hearts of Tgαq*44 and FVB mice. Cardiac function was analyzed in vivo (MRI).

Results

In Tgαq*44 mice at the age of 2–4 months cardiac function was preserved and there were no alterations in endothelial function. By contrast, in Tgαq*44 mice at the age of 14–16 months cardiac function was significantly impaired and NO, but not PGI₂-dependent coronary function was altered. Interestingly, the basal level of PGI₂ in coronary circulation increased fourfold as compared to FVB mice. Cardiac O₂ ⁻ production increased 1.5-fold and 3-fold in Tgαq*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 PGI₂ production in Tgαq*44 mice. There was also an increased expression of gp91phox in Tgαq*44 vs. FVB hearts, without evident alterations in the expression of COX-1, COX-2, NOS-3 and PGI₂-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 PGI₂. Both the decrease in NO activity and the increase in PGI₂ activity may result from excessive O₂ ⁻ production by cardiac NADPH oxidase in Tgαq*44 hearts.

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Title: NO and PGI2 in coronary endothelial dysfunction in transgenic mice with dilated cardiomyopathy
Authors: 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
Publication date: 01-09-2008
Publisher: D. Steinkopff-Verlag
Published in: Basic Research in Cardiology / Issue 5/2008
Print ISSN: 0300-8428
Electronic ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-008-0723-2

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