Objective: To investigate the contribution of angiotensin II towards the process of hepatic fibrosis that is largely due to hepatic stellate cell growth. Methods: Adult rat hepatic stellate cells were cultured and checked for the expression of angiotensin II receptor 1a (AT1a) mRNA by RT-PCR and sequence analysis. The effects of angiotensin II were observed on stimulation of hepatic stellate cell growth detected by MTT assays, 3H-thymidine incorporation and cell count, and collagen synthesis by 3H-proline incorporation. Results: We demonstrated that cultured adult rat hepatic stellate cells expressed AT1a mRNA, and angiotensin II in a concentration-dependent manner stimulated hepatic stellate cell growth at a concentration of 10–7–10–9 mol/l and collagen synthesis at a concentration of 10–6–10–10 mol/l. Also, AT1a receptor antagonist, in a concentration-dependent manner, blocked the cell growth from 10–6 to 10–8 mol/l and collagen synthesis from 10–6 to 10–9 mol/l. Conclusions: The results provided direct evidence that AT1a mRNA was expressed in rat hepatic stellate cells and angiotensin II could contribute towards the development of hepatic fibrosis via AT1a receptor.

Keywords:
AT1a mRNA, DNA sequence, Ang II, Losartan, Hepatic fibrosis
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2003
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