Possible mechanisms involved in the discrepancy of hepatic and aortic endothelial nitric oxide synthases during the development of cirrhosis in rats.
OBJECTIVE
In cirrhosis, systemic nitric oxide (NO) overproduction and hepatic NO hypoproduction lead to arterial vasodilatation and portal hypertension. The mechanisms involved in these alterations in endothelial NO synthase (eNOS)-derived NO production in hepatic and systemic vasculature remain unknown. The aim of this study was to evaluate the regulation of eNOS and its major modulators in the liver and aorta during the development of cirrhosis in rats.


METHODS
Activated eNOS and Akt and expressions, and caveolin-1 (Cav-1) and scavenger receptor class B type I (SR-BI) expressions were measured before and 1, 2, 3 and 4 weeks after bile duct ligation. Plasma high-density lipoprotein (HDL) levels were measured.


RESULTS
Activated aortic eNOS increased at week 1, whereas it began to decrease at week 3 in the liver. Aortic expression of Cav-1 decreased at week 3 while hepatic expression increased by four-fold. Activated aortic Akt increased progressively while in the liver it gradually decreased during the development of cirrhosis. HDL levels decreased during the first week and decreased thereafter. The hepatic expression of SR-BI decreased.


CONCLUSIONS
This study shows that the modulation of Akt and Cav-1 is inverted in the liver and the aorta during the development of cirrhosis. In addition, decreased HDL levels may play a role in reduced hepatic eNOS activity.
Mohammadi
Morvarid Shir
MS
INSERM, U773, Centre de Recherche Biomédical Bichat-Beaujon, Hôpital Beaujon, Clichy, France.
Thabut
Dominique
D
Cazals-Hatem
Dominique
D
Galbois
Arnaud
A
Rudler
Marika
M
Bonnefont-Rousselot
Dominique
D
Moreau
Richard
R
Lebrec
Didier
D
Tazi
Khalid A
KA
D000704:Analysis of Variance; D000818:Animals; D001011:Aorta / Q000378:metabolism*; D015153:Blotting, Western; D051242:Caveolin 1 / Q000378:metabolism; D007150:Immunohistochemistry; D008075:Lipoproteins, HDL / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D051381:Rats; D051122:Scavenger Receptors, Class B / Q000378:metabolism; D013997:Time Factors
C495537:Cav1 protein, rat; D051242:Caveolin 1; D008075:Lipoproteins, HDL; C495125:Scarb1 protein, rat; D051122:Scavenger Receptors, Class B; D052250:Nitric Oxide Synthase Type III