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

Moonyoung Kim, Soonkoo Baik, Dong Hun Park, Yoon Ok Jang, Ki Tae Suk, Chang Jin Yea, Il Young Lee, Jae Woo Kim, Hyunsoo Kim, Sang Ok Kwon, Meeyon Cho, Sang Baik Ko, Sei Jin Chang, Soon Ho Um, KwangHyub Han

Research output: Contribution to journalArticle

38 Citations (Scopus)

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

Fingerprint

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

All Science Journal Classification (ASJC) codes

  • Gastroenterology

Cite this

Kim, Moonyoung ; Baik, Soonkoo ; Park, Dong Hun ; Jang, Yoon Ok ; Suk, Ki Tae ; Yea, Chang Jin ; Lee, Il Young ; Kim, Jae Woo ; Kim, Hyunsoo ; Kwon, Sang Ok ; Cho, Meeyon ; Ko, Sang Baik ; Chang, Sei Jin ; Um, Soon Ho ; Han, KwangHyub. / 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.
@article{01bdf29cec9b4d22b1dfa81dc895f8ae,
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. 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.",
author = "Moonyoung Kim and Soonkoo Baik 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 Hyunsoo Kim and Kwon, {Sang Ok} and Meeyon Cho and Ko, {Sang Baik} and Chang, {Sei Jin} and Um, {Soon Ho} and KwangHyub Han",
year = "2008",
month = "11",
day = "28",
doi = "10.1007/s00535-008-2239-9",
language = "English",
volume = "43",
pages = "889--896",
journal = "Journal of Gastroenterology",
issn = "0944-1174",
publisher = "Springer Japan",
number = "11",

}

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

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

Research output: Contribution to journalArticle

TY - JOUR

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, Moonyoung

AU - Baik, Soonkoo

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, Hyunsoo

AU - Kwon, Sang Ok

AU - Cho, Meeyon

AU - Ko, Sang Baik

AU - Chang, Sei Jin

AU - Um, Soon Ho

AU - Han, KwangHyub

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.

UR - http://www.scopus.com/inward/record.url?scp=56649106258&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=56649106258&partnerID=8YFLogxK

U2 - 10.1007/s00535-008-2239-9

DO - 10.1007/s00535-008-2239-9

M3 - Article

VL - 43

SP - 889

EP - 896

JO - Journal of Gastroenterology

JF - Journal of Gastroenterology

SN - 0944-1174

IS - 11

ER -