[The effect of angiotensin II type 1 receptor blocker valsartan in preventing hepatic fibrosis induced by dimethylnitrosamine in rats].
OBJECTIVE
To observe the effects of angiotensin II type 1 receptor blocker valsartan in preventing hepatic fibrosis induced by dimethylnitrosamine in rats.


METHODS
Except rats in the control group, all were given intraperitoneal injections of 1% dimethylnitrosamine (DMN 1 ml/kg, two or three consecutive days/a week for 6 weeks). From the first day of the intraperitoneal injection, rats in treatment groups were given valsartan for 8 weeks by gastric gavage. Liver tissue and blood samples of all rats were examined at 56 days (8 weeks). AngII levels were determined by radioimmunoassay. Hepatic mRNA levels of Collagen type I (Col I) and tissue inhibitor of metalloproteinase1 (TIMP1) were evaluated by reverse-transcription polymerase chain reaction (RT-PCR).


RESULTS
Valsartan significantly attenuated the degree of liver fibrosis and decreased the hepatic AngII content compared with DMN treated rats (P<0.01). mRNA levels of Col I and TIMP1 were upregulated in DMN treated rats compared with normal rats. Valsartan downregulated the elevation of Col I and TIMP1 mRNA levels (P<0.01).


CONCLUSIONS
Hepatic AngII content of the model group was increased, the local tissue RAS was activated in DMN induced liver fibrosis. Valsartan can retard the progression of hepatic fibrosis and may provide an effective new strategy for anti-liver fibrosis therapy.
Shen
Feng-jun
FJ
Beijing Friendship Hospital, Capital University of Medical Science, Beijing 100050, China.
Zhu
Yue-ke
YK
Jia
Ji-dong
JD
Ma
Hong
H
Wang
Bao-en
BE
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D004128:Dimethylnitrosamine; D005260:Female; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000068756:Valsartan
D047228:Angiotensin II Type 1 Receptor Blockers; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine; D004128:Dimethylnitrosamine