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Abstract
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.
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.
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.
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.