Background and aims: There is a significant relationship between inheritance of high transforming growth factor (TGF)-beta1 and angiotensinogen-producing genotypes and the development of progressive hepatic fibrosis in patients with chronic hepatitis C. In cardiac and renal fibrosis, TGF-beta1 production may be enhanced by angiotensin II, the principal effector molecule of the renin-angiotensin system. The aim of the present study was to determine the effects of the angiotensin-converting enzyme inhibitor, captopril, on the progression of hepatic fibrosis in the rat bile duct ligation model.
Methods: Rats were treated with captopril (100 mg. kg(-1). day(-1)) commencing 1 or 2 weeks after bile duct ligation. Animals with bile duct ligation only and sham-operated animals served as controls. Four weeks after bile duct ligation, indices of fibrosis were assessed.
Results: Captopril treatment significantly reduced hepatic hydroxyproline levels, mean fibrosis score, steady state messenger RNA levels of TGF-beta1 and procollagen alpha1(I), and matrix metalloproteinase 2 and 9 activity.
Conclusions: Captopril significantly attenuates the progression of hepatic fibrosis in the rat bile duct ligation model, and its effectiveness should be studied in human chronic liver diseases associated with progressive fibrosis.