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J Hepatol. 2001 Sep;35(3):376-85.

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

Author information

1
Department of Medicine, University of Melbourne, Austin and Repatriation Medical Centre Melbourne, Australia. gpaizis@austin.unimelb.edu.au

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-beta1 and alpha1 (I) collagen in the liver. TGF-beta1 and alpha1 (I) collagen mRNA expression and localisation were also assessed by in situ hybridisation. TGF-beta1 activity was assessed by using the TGF-beta inducible gene product betaig-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-beta1, betaig-h3 and alpha1 (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.

PMID:
11592599
DOI:
10.1016/s0168-8278(01)00146-5
[Indexed for MEDLINE]

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