Angiotensin-converting enzyme inhibition attenuates the progression of rathepatic fibrosis

Background & Aims: There is a significant relationship between inheritance of high transforming growth factor (TGF)-beta1 and angiotensinogen-producin g genotypes and the development of progressive hepatic fibrosis in patients with chronic hepatitis C. In cardiac and renal fibrosis, TGF-beta1 product ion may be enhanced by angiotensin II, the principal effector molecule of t he renin-angiotensin system. The aim of the present study was to determine the effects of the angiotensin converting enzyme inhibitor, captopril, on t he progression of hepatic fibrosis in the rat bile duct ligation model. Met hods: 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 sewed as controls. Four weeks after bile duct lig ation, indices of fibrosis were assessed. Results: Cap topril treatment sig nificantly reduced hepatic hydroxyproline levels, mean fibrosis score, stea dy state messenger RNA levels of TGF-beta1 and procollagen alpha1(I), and m atrix metalloproteinase 2 and 9 activity. Conclusions: Captopril significan tly attenuates the progression of hepatic fibrosis in the vat bile duct lig ation model, and its effectiveness should be studied in human chronic liver diseases associated with progressive fibrosis.