Effects Of Angiotensin Ⅱ And Captopril, Valsartan On The Fibrinolytic Banlance Of Human Umbilical Vein Endothelial Cells

Objective To observe the effects of angiotensin II(AngII), angiotensinconverting enzyme inhibitor(ACEI)--captopril, and a specific type 1angiotensin II receptor(AT1) antagonist--valsartan on plasminogen activatorinhibitor-1(PAI-1) and tissue type plasminogen activator(t-PA) releasing andtheir activity in cultured human umbilical vein endothelial cells(HUVECs).Methods Several groups of cultured HUVECs were incubated with AngII of10-6~10-9mol/L for 24 hours or with 10-6 mol/L AngII for various times up to24 hours. In other groups of HUVECs, captopril and valsartan were addedrespectively to the culture medium with or without AngII for 24 hours. Thenthe antigens and activity of PAI-1and t-PA in the cultured medium weremeasured by enzyme linked immunosorbent assay(ELISA) and the indirectchromogenic assay. Results 10-9~10-6mol/L AngII could markly induce theincrease of PAI-1antigen 144.67 7.00 vs 83.33 10.56, P<0.05 10-9mol/L and activity (8.33 0.29 vs 7.53 0.33, P<0.01 10-9 mol/L) in adose- dependent manner compared to control the increase of t-PA antigeninduced by AngII were less than PAI-1( P<0.01). Various concentration ofAngII had no effect on t-PA activity 0.98 0.05 vs 0.95 0.08,P>0.05 .When HUVECs were cultured with 10-6mol/L AngII for 0~24h,PAI-1antigen 68.00 8.00 vs 9.67 1.86, P<0.01, 4h and activity (2.900.25 vs 1.07 0.44, P<0.01,4h) were increased in a time- dependent mannercompared to control; t-PA activity had no change 1.00 0.05 vs 1.000.04 ,P>0.05 . Valsartan could inhibited the increase of PAI-1 induced byAngII (212.67 5.38 vs 290 6.57, P<0.01) and PAI-1 produced byHUVECs without AngII(96.67 10.25 vs 156 17.34,P<0.01)compared tocontrol . Conclusion AngII stimulated PAI-1 and t-PA releasing, but the IIIlevels of PAI-1 were increased much more than those of t-PA. The activityof t-PA were not increased by AngII. AT1 blocker, valsartan inhibited theeffects of AngII on the release of PAI-1. Our findings suggest that AngII maytake part in some pathogenesis of thromb by decreasing fibrinolytic activity.Valsartan may have some anti-thromb effect by blocking type 1 AngIIreceptor.