Angiotensin-converting enzyme inhibition attenuates the progression of rat hepatic fibrosis.
OBJECTIVE
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.
Jonsson
J R
JR
Department of Surgery, The University of Queensland, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Queensland, Australia. J.Jonsson@mailbox.uq.edu.au
Clouston
A D
AD
Ando
Y
Y
Kelemen
L I
LI
Horn
M J
MJ
Adamson
M D
MD
Purdie
D M
DM
Powell
E E
EE
D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001652:Bile Ducts / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology / Q000627:therapeutic use*; D018076:DNA, Complementary / Q000302:isolation & purification; D008026:Ligation; D008103:Liver Cirrhosis / Q000201:enzymology / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000302:isolation & purification; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000378:metabolism*
D000806:Angiotensin-Converting Enzyme Inhibitors; D018076:DNA, Complementary; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D002216:Captopril