Bataller R, Ginès P, Nicolás J M, Görbig M N, Garcia-Ramallo E, Gasull X, Bosch J, Arroyo V, Rodés J
Liver Unit, Barcelona, Spain.
Gastroenterology. 2000 Jun;118(6):1149-56. doi: 10.1016/s0016-5085(00)70368-4.
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.
The presence of ANGII receptors was assessed by binding studies. The effects of ANGII on intracellular calcium concentration (Ca(2+)), 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+) 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.
血管紧张素II（ANGII）是一种强大的血管收缩因子，其循环水平在慢性肝病中常升高。在这些情况下，肝星状细胞（HSCs）增殖并获得收缩特性。本研究调查了ANGII受体在体外培养的活化人HSCs中的存在情况以及ANGII的作用。
通过结合研究评估ANGII受体的存在情况。还评估了ANGII对细胞内钙浓度（Ca(2+)）、细胞收缩和细胞增殖的影响。
结合研究显示存在AT1亚型的ANGII受体。ANGII引起Ca(2+)和细胞收缩显著的剂量依赖性增加。此外，ANGII刺激DNA合成并增加细胞数量。所有这些作用均被氯沙坦完全阻断，一氧化氮供体或前列腺素E(2)可使其减弱。在静止细胞（培养2天）中几乎检测不到ANGII的作用，这表明HSCs的表型转化与ANGII作用的显著增加有关。
ANGII通过作用于AT1受体诱导人活化HSCs收缩并具有促有丝分裂作用。这些结果表明活化的HSCs是肝内循环中ANGII血管收缩作用的靶点。
