Angiotensin receptor blockers are superior to angiotensin-converting enzyme inhibitors in the suppression of hepatic fibrosis in a bile duct-ligated rat model.
BACKGROUND
Angiotensin blockade such as with an angiotensin II receptor blocker (ARB) or angiotensinconverting enzyme inhibitor (ACEI) has antifibrotic properties. The aim of this study was to evaluate and compare the antifibrotic effect between ARBs and ACEIs.


METHODS
Common bile duct-ligated (BDL) adult Sprague-Dawley rats were allocated to five groups (each group, n = 8) as follows: G1, BDL without drug; G2, BDL + captopril 100 mg/kg per day; G3, BDL + ramipril 10 mg/kg per day; G4, BDL + losartan 10 mg/kg per day; G5, BDL + irbesartan 15 mg/kg per day. Four weeks post-BDL, hepatic fibrosis was analyzed histomorphologically using Batts and Ludwig scores. alpha-Smooth muscle actin (alpha-SMA) expression by immunohistochemical staining, hydroxyproline contents of liver tissue by spectrophotometry, and angiotensin receptor, collagen, procollagen, and transforming growth factor beta (TGF-beta) expressions were evaluated by real-time reverse transcriptase-polymerase chain reaction. Angiotensin receptor expression was also determined by Western blotting.


RESULTS
Batts and Ludwig scores were 3.8, 2.6, 2.4, 1.8, and 1.6 in G1, G2, G3, G4, and G5, respectively. Histologically, ARB groups (G4, G5) showed significant suppression of hepatic fibrosis compared with ACEI groups or the control. Expressions of alpha-SMA (%) and the content of hydroxyproline (microg liver tissue) were significantly lower in ARB groups (G4, G5) than in ACEI groups (G2, G3) (P < 0.05). Also, ARB reduced the expression of angiotensin receptor, collagen, procollagen, and TGF-beta1 compared with ACEI. Western blot analysis showed that the expression of angiotensin receptor was inhibited in both ARB and ACEI groups.


CONCLUSIONS
Both ARB and ACEI attenuate hepatic fibrosis through inhibiting hepatic stellate cell activation, and the inhibitory effect of ARBs on hepatic fibrosis is superior to that of ACEIs in the BDL rat model.
Kim
Moon Young
MY
Department of Internal Medicine and Institute of Lifelong Health, Yonsei University Wonju College of Medicine, 162 Ilsan-dong, Wonju 220-701, South Korea.
Baik
Soon Koo
SK
Park
Dong Hun
DH
Jang
Yoon Ok
YO
Suk
Ki Tae
KT
Yea
Chang Jin
CJ
Lee
Il Young
IY
Kim
Jae Woo
JW
Kim
Hyun Soo
HS
Kwon
Sang Ok
SO
Cho
Mi Yun
MY
Ko
Sang Baik
SB
Chang
Sei Jin
SJ
Um
Soon Ho
SH
Han
Kwang-Hyub
KH
D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D015153:Blotting, Western; D003135:Common Bile Duct / Q000601:surgery; D018450:Disease Progression; D005786:Gene Expression Regulation; D006909:Hydroxyproline / Q000378:metabolism; D007150:Immunohistochemistry; D008026:Ligation; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D012313:RNA / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000096:biosynthesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013053:Spectrophotometry
D047228:Angiotensin II Type 1 Receptor Blockers; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D011945:Receptors, Angiotensin; D012313:RNA; D007703:Peptidyl-Dipeptidase A; D006909:Hydroxyproline