Abstract:
BACKGROUND & AIMS:Circulating levels of angiotensin II (ANGII), a powerful vasoconstrictor factor, are frequently increased in chronic liver diseases. In these conditions, hepatic stellate cells (HSCs) proliferate and acquire contractile properties. This study investigated the presence of receptors for ANGII and the effects of ANGII in human HSCs activated in culture. METHODS:The presence of ANGII receptors was assessed by binding studies. The effects of ANGII on intracellular calcium concentration ([Ca(2+)](i)), cell contraction, and cell proliferation were also assessed. RESULTS:Binding studies showed the presence of ANGII receptors of the AT1 subtype. ANGII elicited a marked dose-dependent increase in [Ca(2+)](i) and cell contraction. Moreover, ANGII stimulated DNA synthesis and increased cell number. All these effects were totally blocked by losartan and reduced by nitric oxide donors or prostaglandin E(2). The effects of ANGII were barely detectable in quiescent cells (2 days in culture), suggesting that phenotypic transformation of HSCs is associated with a marked increase in the effects of ANGII. CONCLUSIONS:ANGII induces contraction and is mitogenic for human-activated HSCs by acting through AT1 receptors. These results suggest that activated HSCs are targets of the vasoconstrictor action of ANGII in the intrahepatic circulation.
journal_name
Gastroenterologyjournal_title
Gastroenterologyauthors
Bataller R,Ginès P,Nicolás JM,Görbig MN,Garcia-Ramallo E,Gasull X,Bosch J,Arroyo V,Rodés Jdoi
10.1016/s0016-5085(00)70368-4keywords:
subject
Has Abstractpub_date
2000-06-01 00:00:00pages
1149-56issue
6eissn
0016-5085issn
1528-0012pii
S0016508500676655journal_volume
118pub_type
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