title: Angiotensin receptor blockers are superior to angiotensin-converting enzyme inhibitors in the suppression of hepatic fibrosis in a bile duct-ligated rat model.
abstract: 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.
authors.affiliation: Department of Internal Medicine and Institute of Lifelong Health, Yonsei University Wonju College of Medicine, 162 Ilsan-dong, Wonju 220-701, South Korea.
authors.forename: Moon Young
authors.initials: MY
authors.lastname: Kim
authors.forename: Soon Koo
authors.initials: SK
authors.lastname: Baik
authors.forename: Dong Hun
authors.initials: DH
authors.lastname: Park
authors.forename: Yoon Ok
authors.initials: YO
authors.lastname: Jang
authors.forename: Ki Tae
authors.initials: KT
authors.lastname: Suk
authors.forename: Chang Jin
authors.initials: CJ
authors.lastname: Yea
authors.forename: Il Young
authors.initials: IY
authors.lastname: Lee
authors.forename: Jae Woo
authors.initials: JW
authors.lastname: Kim
authors.forename: Hyun Soo
authors.initials: HS
authors.lastname: Kim
authors.forename: Sang Ok
authors.initials: SO
authors.lastname: Kwon
authors.forename: Mi Yun
authors.initials: MY
authors.lastname: Cho
authors.forename: Sang Baik
authors.initials: SB
authors.lastname: Ko
authors.forename: Sei Jin
authors.initials: SJ
authors.lastname: Chang
authors.forename: Soon Ho
authors.initials: SH
authors.lastname: Um
authors.forename: Kwang-Hyub
authors.initials: KH
authors.lastname: Han
mesh_terms: 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
chemical_list: 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