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Journal of Gastroenterology

, Volume 43, Issue 11, pp 889–896 | Cite as

Angiotensin receptor blockers are superior to angiotensin-converting enzyme inhibitors in the suppression of hepatic fibrosis in a bile duct-ligated rat model

  • Moon Young Kim
  • Soon Koo Baik
  • Dong Hun Park
  • Yoon Ok Jang
  • Ki Tae Suk
  • Chang Jin Yea
  • Il Young Lee
  • Jae Woo Kim
  • Hyun Soo Kim
  • Sang Ok Kwon
  • Mi Yun Cho
  • Sang Baik Ko
  • Sei Jin Chang
  • Soon Ho Um
  • Kwang-Hyub Han
Liver, Pancreas, and Biliary Tract

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. α-Smooth muscle actin (α-SMA) expression by immunohistochemical staining, hydroxyproline contents of liver tissue by spectrophotometry, and angiotensin receptor, collagen, procollagen, and transforming growth factor β (TGF-β) 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 α-SMA (%) and the content of hydroxyproline (μg 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-β1 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.

Key words

hepatic fibrosis hepatic stellate cell angiotensin II receptor blocker angiotensin converting enzyme inhibitor 

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Copyright information

© Springer Japan 2008

Authors and Affiliations

  • Moon Young Kim
    • 1
  • Soon Koo Baik
    • 1
  • Dong Hun Park
    • 1
  • Yoon Ok Jang
    • 1
  • Ki Tae Suk
    • 1
  • Chang Jin Yea
    • 1
  • Il Young Lee
    • 1
  • Jae Woo Kim
    • 1
  • Hyun Soo Kim
    • 1
  • Sang Ok Kwon
    • 1
  • Mi Yun Cho
    • 2
  • Sang Baik Ko
    • 3
  • Sei Jin Chang
    • 3
  • Soon Ho Um
    • 4
  • Kwang-Hyub Han
    • 5
  1. 1.Department of Internal Medicine and Institute of Lifelong HealthYonsei University Wonju College of MedicineWonjuSouth Korea
  2. 2.Department of PathologyYonsei University Wonju College of MedicineWonjuSouth Korea
  3. 3.Department of Preventive Medicine and Institute of Lifelong HealthYonsei University Wonju College of MedicineWonjuSouth Korea
  4. 4.Department of Internal MedicineKorea University College of MedicineSeoulKorea
  5. 5.Department of Internal MedicineYonsei University College of MedicineSeoulKorea

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