Possible mechanisms involved in the discrepancy of hepatic and aortic endothelial nitric oxide synthases during the development of cirrhosis in rats.

Full Abstract

BACKGROUND/AIM: 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. CONCLUSION: 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.

Author information

Author/s: Mohammadi, Morvarid Shir (MS); 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);

Affiliation: INSERM, U773, Centre de Recherche Biomédical Bichat-Beaujon, Hôpital Beaujon, Clichy, France.

Journal and publication information

Publication Type: Journal Article

Journal: Liver international : official journal of the International Association for the Study of the Liver (Liver Int), published in England. (Language: eng)

Reference: 2009-May; vol 29 (issue 5) : pp 692-700

Dates: Created 2009/05/05; Completed 2009/08/10;

PMID: 19040541, status: MEDLINE (last retrieval date: 8/21/2009, IMS Date: )

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Lipoproteins, HDL - blood
Liver - metabolism
Liver Cirrhosis - metabolism; pathology; physiopathology
Nitric Oxide Synthase Type III - metabolism
Rats
Scavenger Receptors, Class B - metabolism
Time Factors

Associated Chemicals: Cav protein, rat (0) ; Caveolin 1 (0) ; Lipoproteins, HDL (0) ; Scarb1 protein, rat (0) ; Scavenger Receptors, Class B (0) ; Nitric Oxide Synthase Type III (EC 1.14.13.39)

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