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

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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.

Original languageEnglish
Pages (from-to)889-896
Number of pages8
JournalJournal of Gastroenterology
Volume43
Issue number11
DOIs
Publication statusPublished - 2008 Nov 28

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Angiotensin Receptor Antagonists
Bile Ducts
Angiotensin-Converting Enzyme Inhibitors
Enzyme Inhibitors
Fibrosis
Angiotensin Receptors
Liver
Procollagen
irbesartan
Hydroxyproline
Transforming Growth Factors
Collagen
Western Blotting
Ramipril
Hepatic Stellate Cells
Losartan
Spectrophotometry
Captopril
Angiotensins
Common Bile Duct

Keywords

  • Angiotensin converting enzyme inhibitor
  • Angiotensin II receptor blocker
  • Hepatic fibrosis
  • Hepatic stellate cell

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Angiotensin receptor blockers are superior to angiotensin-converting enzyme inhibitors in the suppression of hepatic fibrosis in a bile duct-ligated rat model. / Kim, Moon Young; Baik, Soon Koo; Park, Dong Hun; Jang, Yoon Ok; Suk, Ki Tae; Yea, Chang Jin; Lee, Il Young; Kim, Jae Woo; Kim, Hyun Soo; Kwon, Sang Ok; Cho, Mi Yun; Ko, Sang Baik; Chang, Sei Jin; Um, Soon-Ho; Han, Kwang Hyub.

In: Journal of Gastroenterology, Vol. 43, No. 11, 28.11.2008, p. 889-896.

Research output: Contribution to journalArticle

Kim, MY, Baik, SK, Park, DH, Jang, YO, Suk, KT, Yea, CJ, Lee, IY, Kim, JW, Kim, HS, Kwon, SO, Cho, MY, Ko, SB, Chang, SJ, Um, S-H & Han, KH 2008, 'Angiotensin receptor blockers are superior to angiotensin-converting enzyme inhibitors in the suppression of hepatic fibrosis in a bile duct-ligated rat model', Journal of Gastroenterology, vol. 43, no. 11, pp. 889-896. https://doi.org/10.1007/s00535-008-2239-9
Kim, Moon Young ; Baik, Soon Koo ; Park, Dong Hun ; Jang, Yoon Ok ; Suk, Ki Tae ; Yea, Chang Jin ; Lee, Il Young ; Kim, Jae Woo ; Kim, Hyun Soo ; Kwon, Sang Ok ; Cho, Mi Yun ; Ko, Sang Baik ; Chang, Sei Jin ; Um, Soon-Ho ; Han, Kwang Hyub. / Angiotensin receptor blockers are superior to angiotensin-converting enzyme inhibitors in the suppression of hepatic fibrosis in a bile duct-ligated rat model. In: Journal of Gastroenterology. 2008 ; Vol. 43, No. 11. pp. 889-896.
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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.",
keywords = "Angiotensin converting enzyme inhibitor, Angiotensin II receptor blocker, Hepatic fibrosis, Hepatic stellate cell",
author = "Kim, {Moon Young} and Baik, {Soon Koo} and Park, {Dong Hun} and Jang, {Yoon Ok} and Suk, {Ki Tae} and Yea, {Chang Jin} and Lee, {Il Young} and Kim, {Jae Woo} and Kim, {Hyun Soo} and Kwon, {Sang Ok} and Cho, {Mi Yun} and Ko, {Sang Baik} and Chang, {Sei Jin} and Soon-Ho Um and Han, {Kwang Hyub}",
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T1 - Angiotensin receptor blockers are superior to angiotensin-converting enzyme inhibitors in the suppression of hepatic fibrosis in a bile duct-ligated rat model

AU - Kim, Moon Young

AU - Baik, Soon Koo

AU - Park, Dong Hun

AU - Jang, Yoon Ok

AU - Suk, Ki Tae

AU - Yea, Chang Jin

AU - Lee, Il Young

AU - Kim, Jae Woo

AU - Kim, Hyun Soo

AU - Kwon, Sang Ok

AU - Cho, Mi Yun

AU - Ko, Sang Baik

AU - Chang, Sei Jin

AU - Um, Soon-Ho

AU - Han, Kwang Hyub

PY - 2008/11/28

Y1 - 2008/11/28

N2 - 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.

AB - 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.

KW - Angiotensin converting enzyme inhibitor

KW - Angiotensin II receptor blocker

KW - Hepatic fibrosis

KW - Hepatic stellate cell

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