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

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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17 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)417-430
Number of pages14
JournalBasic Research in Cardiology
Volume103
Issue number5
DOIs
Publication statusPublished - Apr 23 2008
Externally publishedYes

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Keywords

  • Dilated cardiomyopathy
  • Endothelial dysfunction
  • Heart failure
  • Nitric oxide
  • Prostacyclin

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Drelicharz, L., Kozlovski, V., Skorka, T., Heinze-Paluchowska, S., Jasinski, A., Gebska, A., ... Chlopicki, S. (2008). NO and PGI2 in coronary endothelial dysfunction in transgenic mice with dilated cardiomyopathy. Basic Research in Cardiology, 103(5), 417-430. https://doi.org/10.1007/s00395-008-0723-2