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.
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.
Authors: Brenda de Oliveira da Silva; Luciane Carla Alberici; Letícia Ferreira Ramos; Caio Mateus Silva; Marina Bonfogo da Silveira; Carlos R P Dechant; Scott L Friedman; Kumiko Koibuchi Sakane; Letícia Rocha Gonçalves; Karen C M Moraes Journal: Int J Biochem Cell Biol Date: 2018-03-07 Impact factor: 5.085
Authors: Walkíria Wingester Vilas-Boas; Antônio Ribeiro-Oliveira; Renata da Cunha Ribeiro; Renata Lúcia Pereira Vieira; Jerusa Almeida; Ana Paula Nadu; Ana Cristina Simões e Silva; Robson Augusto Souza Santos Journal: World J Gastroenterol Date: 2008-11-28 Impact factor: 5.742
Authors: Regina Maria Pereira; Robson Augusto Souza dos Santos; Filipi Leles da Costa Dias; Mauro Martins Teixeira; Ana Cristina Simões e Silva Journal: World J Gastroenterol Date: 2009-06-07 Impact factor: 5.742
Authors: Regina M Pereira; Robson A S dos Santos; Eduardo A Oliveira; Virginia H R Leite; Filipi L C Dias; Alysson S Rezende; Lincoln P Costa; Luciola S Barcelos; Mauro M Teixeira; Ana Cristina Simoes e Silva Journal: World J Gastroenterol Date: 2008-07-28 Impact factor: 5.742