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Angiotensin‐II type 1 receptor interaction is a major regulator for liver fibrosis development in rats
Author(s) -
Yoshiji Hitoshi,
Kuriyama Shigeki,
Yoshii Junichi,
Ikenaka Yasuhide,
Noguchi Ryuichi,
Nakatani Toshiya,
Tsujinoue Hirohisa,
Fukui Hiroshi
Publication year - 2001
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1053/jhep.2001.28231
Subject(s) - hepatic stellate cell , angiotensin ii , endocrinology , medicine , hepatic fibrosis , candesartan , fibrosis , in vivo , receptor , transforming growth factor , renin–angiotensin system , chemistry , biology , microbiology and biotechnology , blood pressure
The renin‐angiotensin system (RAS) is frequently activated in patients with chronic liver diseases. Angiotensin‐II (AT‐II) has been suggested to play an important role in liver fibrogenesis. It induces hepatic stellate cell (HSC) proliferation and up‐regulates the transforming growth factor β 1 (TGF‐β 1 ) expression via AT‐II type 1 receptor (AT 1 ‐R) in vitro. The aim of the present study was to examine the in vivo effect of candesartan (CA), a clinically used AT 1 ‐R blocker (ARB), and perindopril (PE), an angiotensin‐converting enzyme (ACE) inhibitor (ACE‐I), on pig serum‐induced liver fibrosis development in rats. The clinically available comparable doses of CA and PE significantly attenuated the fibrosis development. These inhibitory effects of PE and CA were also found in the on‐going liver fibrosis model. The hepatic hydroxyproline and serum fibrosis markers were significantly suppressed by CA and PE treatment. Furthermore, the α smooth muscle actin (α‐SMA) positive cells in number were markedly suppressed by CA and PE treatment. Similarly, the hepatic TGF‐β 1 protein and messenger RNA (mRNA) levels were significantly suppressed. Our in vitro study showed that AT‐II increased the TGF‐β 1 mRNA expression in the activated HSCs, and this effect was totally blocked by CA. These results suggested that the RAS, especially AT‐II and AT 1 ‐R interaction plays a pivotal role in liver fibrosis development through HSC activation. Because both CA and PE are widely used in clinical practice without serious side effects, these drugs may provide an effective new strategy for anti–liver fibrosis therapy.