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Dual blockade of angiotensin‐ II and aldosterone suppresses the progression of a non‐diabetic rat model of steatohepatitis
Author(s) -
Noguchi Ryuichi,
Yoshiji Hitoshi,
Ikenaka Yasuhide,
Kaji Kosuke,
Aihara Yosuke,
Shirai Yusaku,
Namisaki Tadashi,
Kitade Mitsuteru,
Douhara Akitoshi,
Moriya Kei,
Fukui Hiroshi
Publication year - 2013
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/hepr.12008
Subject(s) - blockade , aldosterone , angiotensin ii , steatohepatitis , medicine , angiotensin 1 , renin–angiotensin system , endocrinology , dual (grammatical number) , diabetes mellitus , receptor , disease , fatty liver , art , literature , blood pressure
Aim Both angiotensin‐ II ( AT‐II ) and aldosterone ( A ld) play pivotal roles in the pathogenesis of diseases in several organs including the liver. We previously reported that suppression of AT‐II and A ld with angiotensin‐converting enzyme inhibitor ( ACE ‐ I ) and selective A ld blocker ( SAB ), respectively, attenuated the rat liver fibrogenesis and hepatocarcinogenesis. The aim of our current study was to elucidate the combined effects of ACE ‐ I and SAB in the progression of a non‐diabetic rat model of steatohepatitis, and the possible mechanisms involved. Methods In the choline‐deficient L‐amino acid‐defined ( CDAA ) diet‐induced model, the effects of ACE ‐ I and SAB on liver fibrosis development and hepatocarcinogenesis were elucidated, especially in conjunction with neovascularization. Results Treatment with both ACE ‐ I and SAB suppressed the development of liver fibrosis and glutathione‐ S ‐transferase placental form ( GST ‐ P ) positive pre‐neoplastic lesions. The combined treatment with both agents exerted more inhibitory effects as compared with either a single agent along with suppression of the activated hepatic stellate cells ( A c‐ HSC ) and neovascularization, both of which play important roles in these processes. Our in vitro study showed that AT‐II type 1 receptor blocker ( ARB ) and SAB inhibited A c‐ HSC proliferation and in vitro angiogenesis along with suppression of the in vivo studies. Conclusion Dual blockade of AT‐II and A ld suppresses the progression of a non‐diabetic rat model of steatohepatitis. Because both agents are widely and safely used in clinical practice, this combination therapy could be an effective new strategy against steatohepatitis in the future.