[Inhibitory effect of angiotensin blockade on hepatic fibrosis in common bile duct-ligated rats].
OBJECTIVE
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.


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 (microg/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.
Park
Dong Hun
DH
Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.
Baik
Soon Koo
SK
Choi
Yeon Hee
YH
Kim
Moon Young
MY
Rhim
Dae Wook
DW
Kim
Jae Woo
JW
Kwon
Sang Ok
SO
Cho
Mi Yun
MY
Kim
Chul Han
CH
Ahn
Seung Chan
SC
D000199:Actins / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001652:Bile Ducts / Q000473:pathology / Q000601:surgery; D002216:Captopril / Q000008:administration & dosage / Q000627:therapeutic use*; D005355:Fibrosis; D006909:Hydroxyproline / Q000378:metabolism; D008026:Ligation; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D019808:Losartan / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000378:metabolism
D000199:Actins; D047228:Angiotensin II Type 1 Receptor Blockers; D016212:Transforming Growth Factor beta; D002216:Captopril; D019808:Losartan; D006909:Hydroxyproline