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

Background/Aims: The aim of this study was to investigate whether in the li ver, as in other tissues, there is evidence that angiotensin II, acting via the angiotensin II type I receptor (ATI-R), plays a role in fibrogenesis. Methods: Sprague-Dawley rats were divided into three groups; sham, bile duc t ligated (BDL) and BDL + AT1-R antagonist, irbesartan. Real time RT-PCR wa s utilised to assess gene expression of the AT1 receptor, TGF-beta1 and alp ha1 (I) collagen in the liver. TGF-beta1 and alpha1 (I) collagen mRNA expre ssion and localisation were also assessed by in situ hybridisation. TGF-bet a1 activity was assessed by using the TGF-beta inducible gene product beta ig-h3. Fibrosis was assessed by the Knodell scoring system, tissue hydroxyp roline content and picro-sirius red staining. Results: Real time RT-PCR revealed that there was a 6-fold up-regulation in ATI receptor expression in BDL animals compared with shams. This was assoc iated with marked increases in TGF-beta1, beta ig-h3 and alpha1 (1) collage n gene expression which were attenuated by AT1-RA treatment. However, AT1-R A therapy produced no significant change in liver histology or hydroxyproli ne content. Conclusions: These results suggest that in the liver angiotensin II may pla y an important role in the fibrogenic response to injury. However, whether treatment with an AT1-RA will be of therapeutic benefit remains to be deter mined. (C) 2001 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.