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

J Hepatol. 2001 Sep;35(3):376-85. doi: 10.1016/s0168-8278(01)00146-5.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / physiology
  • Angiotensin Receptor Antagonists*
  • Animals
  • Collagen / genetics
  • Immunohistochemistry
  • In Situ Hybridization
  • Liver Cirrhosis, Experimental / drug therapy*
  • Liver Cirrhosis, Experimental / etiology
  • Liver Cirrhosis, Experimental / metabolism
  • Male
  • RNA, Messenger / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Angiotensin, Type 1
  • Receptors, Angiotensin / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transforming Growth Factor beta / analysis


  • Angiotensin Receptor Antagonists
  • RNA, Messenger
  • Receptor, Angiotensin, Type 1
  • Receptors, Angiotensin
  • Transforming Growth Factor beta
  • Angiotensin II
  • Collagen