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

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 (TGF beta(1)). 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 TGF beta(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. (c) 2006 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.