Effect Of Captopril And Valsartan On Inhibiting The Formation Of Atherosclerosis And The Expression Of AngiotensinⅡ And Plasminogen Activator Inhibitor-1 In Aortoic Plaques Of Atherosclerotic Rabbits

objective To study the effect of angiotensinll (Angll) on the expression of plasminogen activator inhibitor-l(PAI-l), to test the role of angiotensin-converting enzyme inhibition, captopril, and angiotensin II type 1 receptor blockade,valsartan, on development of atherosclerosis and fibrinolytic balance in plaques of atherosclerotic rabbits, to elucidate the relativity between Angll and atherosclerosis and PAI-1, and to demonstrate the effects of antiatherosclerosis and improvement fibrinolytic balance with captopril, and valsartan beyond their antihypertensive action.Methods Thirty male New Zealand white rabbits were study. The rabbits were randomly divided into four groups: (1) cholesterol group (n=8): 1% cholesterol diet ; (2) cholesterol+ captopril treated group (n=8): 1% cholesterol diet supplement captopril(2mg/kg per day); (3) cholesterol+ valsartan treated group (n=8): 1% cholesterol diet supplement valsartan(10mg/kg per day);(4)control group(n=6): normal rabbit chow. After 10 weeks, PAI-1 activity of plasma was evaluated by spectrphotometric assy. Angll level of plasma was measured with competitive radioimmunoassays. The aorta was harvested for histomorphometry observation and the expression of Angll and PAI-1 were showed by immunohistochenistry measure.Result Compared with control group, Angll level, PAI-1 activity and the aortic intimal thinkness increased significantly (P<0.01) in cholesterol group. The percent of Angll-positive and PAI-1-positive cells in plaques were significantly higher ( 46.9814.32% versus 4.17 1.01 %and 48.5 ?13.46% versus 1.33 0.52% respectively, P<0.01).Captopril and valsartan significantly reduced aortic intimal thinkness and PAI-1 activity (P<0.05) compared with cholesterol group. The percent of Angll -positive and PAI-1-positive cells were significantlyIVdecreased in captopril group(26.30?.00% versus 46.97?14.32%and 20.37 ?.23% versus 48.5+13.46% respectively,<0.05) and in valsartan group ( 27.83 + 7.30% versus 46.97+14.32%and22.50 + 7.06% versus 48.5 + 13.46% respectively. P<0.05). The expression of PAI-1 was positively correlated with the expression of Angll in local of atherosclerotic plaques (r=0.796, <0.01). Conclusion Angll is associated with the development of atherosclerosis; The expression of PAI-1 was positively correlated with the expression of Angll in plaques of atherosclerosis; Captopril and valsartan reduced the expression of Angll and PAI-1 in plaque and inhibited the formation of atherosclerosis .