The expression of AT1 receptor on hepatic stellate cells in rat fibrosis induced by CCl4

Objectives To assess the effect of an ACE inhibitor and an Ang IE type 1 (A T1) receptor antagonist on preventing hepatic fibrosis induced by CCl4 in r ats and to investigate whether there is the expression of AT1 receptors on hepatic stellate cells. Methods Studies were conducted in male Sprague-Dawley rats. Except for mode l group and control group, in three treated groups, either enalapril (5 mg/ kg), or losartan (10 mg/kg), or enalapril + losartan were given to the fibr otic rats (daily gavage). Saline vehicle was given to the control group. Af ter 6 weeks, liver fibrosis was assessed directly by hepatic morphometric a nalysis. The expression of AT1 receptors and alpha -smooth muscle actin (al pha -SMA) in liver tissue and isolated hepatic stellate cells (HSC) were de tected by immunohistochemical techniques. Results Compared with the fibrosis in rats of the model group, rats treated with either enalapril or losartan, or a combination of two drugs, showed a limited expansion of the interstitium (P < 0.05), but no significant diffe rence was observed among the three treated groups (P > 0.05). The expressio n of AT1 receptors was found in abundance in the fibrotic interstitium of t he fibrotic rats, whereas in the normal control rats they were limited to t he vascular wall. AT1 receptors were also expressed on activated HSC in cul ture plates. Conclusions Angiotensin-converting enzyme inhibitors and AT-1 blockers migh t slow the progression of hepatic fibrosis. Activated HSCs expressed AT1 re ceptors. Activation of RAS might be related to hepatic fibrogenesis induced by CCl4.