Format

Send to

Choose Destination
J Hepatol. 2007 Apr;46(4):674-81. Epub 2006 Nov 27.

The renin-angiotensin system in a rat model of hepatic fibrosis: evidence for a protective role of Angiotensin-(1-7).

Author information

1
Departamento de Pediatria, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Av. Alfredo Balena, 190, Belo Horizonte, MG 30130-100, Brazil.

Abstract

BACKGROUND/AIMS:

The circulating renin-angiotensin system (RAS) [plasma renin activity (PRA), Angiotensin (Ang) I, Ang II and Ang-(1-7)] was evaluated in a model of hepatic fibrosis in rats. To investigate the pathophysiological involvement of Ang-(1-7), animals were treated with the Ang-(1-7) Mas receptor antagonist, A-779.

METHODS:

RAS components, liver function and histology were examined in male Wistar rats (220-300 g). Animals were submitted to sham-surgery or ligature of the bile duct and evaluated 1, 2, 4 and 6 weeks later. Blood samples were obtained to determine biochemical parameters and RAS components. A second group was treated with A-779 or vehicle to measure liver hydroxyproline and total transforming growth factor beta-1 (TGFbeta1).

RESULTS:

PRA and Ang I were significantly elevated in rats at 4 and 6 weeks compared to sham-operated animals. Ang II and Ang-(1-7) progressively increased over the 6 weeks. Changes in RAS profile correlated with histological signs of fibrosis and deterioration in liver function. Pharmacological blockade of the Ang-(1-7) receptor aggravated liver fibrosis with a significant elevation in hydroxyproline and total TGFbeta(1).

CONCLUSIONS:

Hepatic fibrosis was associated with RAS activation in our model. Our data also suggested that Ang-(1-7) played a protective role in hepatic fibrosis.

PMID:
17188388
DOI:
10.1016/j.jhep.2006.10.018
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center