TY - JOUR
T1 - NO and PGI2 in coronary endothelial dysfunction in transgenic mice with dilated cardiomyopathy
AU - Drelicharz, Lukasz
AU - Kozlovski, Valery
AU - Skorka, Tomasz
AU - Heinze-Paluchowska, Sylwia
AU - Jasinski, Andrzej
AU - Gebska, Anna
AU - Guzik, Tomasz
AU - Olszanecki, Rafal
AU - Wojnar, Leszek
AU - Mende, Ulrike
AU - Csanyi, Gabor
AU - Chlopicki, Stefan
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
KW - Dilated cardiomyopathy
KW - Endothelial dysfunction
KW - Heart failure
KW - Nitric oxide
KW - Prostacyclin
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U2 - 10.1007/s00395-008-0723-2
DO - 10.1007/s00395-008-0723-2
M3 - Article
C2 - 18431525
AN - SCOPUS:50249168743
SN - 0300-8428
VL - 103
SP - 417
EP - 430
JO - Basic Research in Cardiology
JF - Basic Research in Cardiology
IS - 5
ER -