| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 3314698 | Journal of Hepatology | 2007 | 8 Pages |
Background/AimsThe 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.MethodsRAS 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 β-1 (TGFβ1).ResultsPRA 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 TGFβ1.ConclusionsHepatic fibrosis was associated with RAS activation in our model. Our data also suggested that Ang-(1–7) played a protective role in hepatic fibrosis.
