Expression of angiotensin II type 1 receptor in rat hepatic stellate cells and its effects on cell growth and collagen production.

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 (AT(1a)) 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, (3)H-thymidine incorporation and cell count, and collagen synthesis by (3)H-proline incorporation.

Results: We demonstrated that cultured adult rat hepatic stellate cells expressed AT(1a) 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, AT(1a) 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 AT(1a) mRNA was expressed in rat hepatic stellate cells and angiotensin II could contribute towards the development of hepatic fibrosis via AT(1a) receptor.