Effects of angiotensin II and losartan on the growth and proliferation of hepatic stellate cells.
OBJECTIVE
To investigate the effects of angiotensin II (AngII) and AT1a blocker losartan on growth and proliferation of rat hepatic stellate cells (HSCs).


METHODS
Rat HSCs were isolated, cultured and identified, followed by incubation with AngII or losartan at different concentrations. The cell growth and proliferation were assessed via cell counting and MTT assay, and the effects of the agents on HSC DNA synthesis evaluated by way of (3)H-thymidine incorporation ((3)H-TDR).


RESULTS
AngII (1 x 10(-9) to 1 x 10(-7) mol/L) stimulated HSC proliferation as demonstrated by cell counting, MTT assay and thymidine incorporation test (P < 0.05), but such effect was not observed at lower doses (<1 x 10(-9) mol/L). Losartan had significant inhibitory effect on HSC growth at the concentration of 1 x 10(-8) to 1 x 10(-6) mol/L (P < 0.05), but not at lower doses (<1 x 10(-8) mol/L). Co-stimulation of the cells with losartan and AngII did not result in a significant increase in cell number as compared with the control group (P > 0.05).


CONCLUSIONS
Rapid proliferation of rat HSCs occurs in response to AngII treatment, but is inhibited after AT1a receptor is blocked with the antagonist losartan.
Zhang
Yi-jun
YJ
Second Department of Gerontology, Guangzhou General Hospital of Guangzhou Command, Guangzhou 510010, China.
Yang
Xi-shan
XS
Wu
Ping-sheng
PS
Li
Xu
X
Zhang
Xiao-feng
XF
Chen
Xiao-qing
XQ
Yu
Zhong-xun
ZX
D000804:Angiotensin II / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004338:Drug Combinations; D022781:Hepatocytes / Q000187:drug effects* / Q000473:pathology; D008103:Liver Cirrhosis / Q000473:pathology; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D047228:Angiotensin II Type 1 Receptor Blockers; D004338:Drug Combinations; D000804:Angiotensin II; D019808:Losartan