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

• Published in: Journal of hepatology 2007-04, Vol.46 (4), p.674-681
• Main Authors: Pereira, Regina Maria, dos Santos, Robson Augusto Souza, Teixeira, Mauro Martins, Leite, Virginia Hora Rios, Costa, Lincoln Paiva, da Costa Dias, Filipi Leles, Barcelos, Lucíola S, Collares, Guilherme Birchal, Simões e Silva, Ana Cristina
• Format: Article
• Language: English
• Subjects: A-779; Angiotensin I - metabolism; Angiotensin II; Angiotensin II - analogs & derivatives; Angiotensin II - pharmacology; Angiotensin-(1–7); Animals; Biological and medical sciences; Cytoprotection; Gastroenterology and Hepatology; Gastroenterology. Liver. Pancreas. Abdomen; Hydroxyproline - metabolism; Liver - drug effects; Liver - pathology; Liver - physiopathology; Liver Cirrhosis - metabolism; Liver Cirrhosis - pathology; Liver Cirrhosis - physiopathology; Liver injury; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Other diseases. Semiology; Peptide Fragments - metabolism; Peptide Fragments - pharmacology; Proto-Oncogene Proteins - antagonists & inhibitors; Rats; Rats, Wistar; Receptors, G-Protein-Coupled - antagonists & inhibitors; Renin-Angiotensin System; Transforming growth factor; Transforming Growth Factor beta1 - metabolism
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2006.10.018

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 β-1 (TGFβ1 ). 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 TGFβ1. 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.