Effect of angiotensin II type 1 receptor blockade on experimental hepatic fibrogenesis

Abstract

Background/Aims : The aim of this study was to investigate whether in the liver, as in other tissues, there is evidence that angiotensin II, acting via the angiotensin II type 1 receptor (AT1-R), plays a role in fibrogenesis. Methods : Sprague–Dawley rats were divided into three groups; sham, bile duct ligated (BDL) and BDL+AT1-R antagonist, irbesartan. Real time RT-PCR was utilised to assess gene expression of the AT1 receptor, TGF-β1 and α1 (I) collagen in the liver. TGF-β1 and α1 (I) collagen mRNA expression and localisation were also assessed by in situ hybridisation. TGF-β1 activity was assessed by using the TGF-β inducible gene product βig-h3. Fibrosis was assessed by the Knodell scoring system, tissue hydroxyproline content and picro-sirius red staining. Results : Real time RT-PCR revealed that there was a 6-fold up-regulation in AT1 receptor expression in BDL animals compared with shams. This was associated with marked increases in TGF-β1, βig-h3 and α1 (I) collagen gene expression which were attenuated by AT1-RA treatment. However, AT1-RA therapy produced no significant change in liver histology or hydroxyproline content. Conclusions : These results suggest that in the liver angiotensin II may play an important role in the fibrogenic response to injury. However, whether treatment with an AT1-RA will be of therapeutic benefit remains to be determined.