Angiotensin-converting enzyme inhibition attenuates the progression of rat hepatic fibrosis

JR Jonsson, AD Clouston, Y Ando, LI Kelemen… - Gastroenterology, 2001 - Elsevier
JR Jonsson, AD Clouston, Y Ando, LI Kelemen, MJ Horn, MD Adamson, DM Purdie…
Gastroenterology, 2001Elsevier
Background & Aims: There is a significant relationship between inheritance of high
transforming growth factor (TGF)-β1 and angiotensinogen-producing genotypes and the
development of progressive hepatic fibrosis in patients with chronic hepatitis C. In cardiac
and renal fibrosis, TGF-β1 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 …
Background & Aims
There is a significant relationship between inheritance of high transforming growth factor (TGF)-β1 and angiotensinogen-producing genotypes and the development of progressive hepatic fibrosis in patients with chronic hepatitis C. In cardiac and renal fibrosis, TGF-β1 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-β1 and procollagen α1(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.
Elsevier