In this study, we assessed the hypothesis that the expression of angiotensin II receptor type 1 (AGTR1) in liver tissue changes
with increasing fibrosis, which would influence the antifibrotic efficacy of AGTR1 blockers. Rats were treated with candesartancilexetil
(CAN) initiated 8 or 15 days after bile duct occlusion (BDO). Four weeks after BDO, AGTR1 mRNA and protein were decreased
compared to those in sham-operated animals depending on the amount of fibrosis. Starting CAN early, but not late, reduced
mRNA of profibrotic TGF-β, MMP2, and Smad2. However, CAN had no significant effect on collagen I, fibrosis, or intrahepatic
resistance. In conclusion, progression of liver fibrosis reduces AGTR1 expression. Therefore, in our model, antifibrotic effects
of CAN are insufficient to improve fibrosis or intrahepatic resistance. However, if AGTR1 blockade is started early, a decrease
in essential profibrotic molecules is achieved. Hence, early initiation of therapy with AGTR1 blockers may be crucial for
the prevention of cirrhosis.
Keywords Angiotensin II receptor type 1 - Fibrogenesis - Candesartan - Experimental liver cirrhosis - Rats - Bile duct occlusion - Transforming growth factor ß - Smad2 protein