Korean J Hepatol.  2007 Mar;13(1):61-69.

Inhibitory Effect of Angiotensin Blockade on Hepatic Fibrosis in Common Bile Duct-ligated Rats

• Park DH
• Baik SK
• Choi YH
• Kim MY
• Rhim DW
• Kim JW
• Kwon SO
• Cho MY
• Kim CH
• Ahn SC

Abstract

BACKGROUNDS AND AIMS: Angiotensin receptors are found on hepatic stellate cells, which participate in hepatic fibrosis. Therefore, it is presumed that angiotensin has a role in hepatic fibrosis. The aim of this study was to evaluate the effects of angiotensin blockade on inhibition of hepatic fibrosis in cirrhotic rat model. Material and METHODS: Cirrhosis with portal hypertension was produced by common bile duct ligation (BDL) in the adult Sprague-Dawley rats. They were classified into 4 groups (each group n=6) as follows; G1: BDL without drug, G2: BDL+captopril 100 mg/kg/day beginning 2 weeks after BDL, G3: BDL+captopril 100 mg/kg/day, starting just after BDL, G4: BDL+losartan 10 mg/kg/day, starting just after BDL. After 4 weeks following BDL, hepatic fibrosis was histomorphologically analyzed by Batts & Ludwig score. Alpha smooth muscle actin by immunohistochemical stain, hydroxyproline contents of liver tissue by spectrophotometry and expression of collagen, procollagen, and TGF-beta by real-time PCR were measured. RESULTS: Batts & Ludwig score were 3.8, 3.0, 2.6,and 2.6 in G1, G2, G3, and G4, respectively. The expression of alpha-SMA was significantly lower in G3 and G4 than in G1; 11.9%, 10.9%, 2.6%, and 1.1% in G1, G2, G3, and G4, respectively (p<0.05). The concentration of hydroxyproline (microgram/g liver tissue) was lower in G3 and G4 compared with G1 (p<0.05). Also, the administration of angiotensin blockade just after BDL significantly reduced the expression of collagen, procollagen, and TGF-beta mRNA. CONCLUSIONS: Angiotensin blockades are effective in the prevention of hepatic fibrosis in BDL rats.

Keyword

Fibrosis; Angiotensin-converting enzyme inhibitors; Angiotensin II type I receptor blockers; Liver; Rats

MeSH Terms

Actins/metabolism
Angiotensin II Type 1 Receptor Blockers/administration & dosage/*therapeutic use
Animals
Bile Ducts/pathology/surgery
Captopril/administration & dosage/*therapeutic use
Fibrosis
Hydroxyproline/metabolism
Ligation
Liver/drug effects/metabolism/pathology
Liver Cirrhosis, Experimental/*drug therapy/etiology/metabolism
Losartan/administration & dosage/*therapeutic use
Male
Rats
Rats, Sprague-Dawley
Transforming Growth Factor beta/metabolism