AIM:To investigate mechanism and effects of losartan and captopril on the fibrinolytic function and formation of experimental atherosclerosis in cholesterol fed rabbits. METHODS: Forty healthy male rabbits were randomly divided into four groups. Group A received normal chow, group B,C,D were submitted to 1 % cholesterol and 5 % lard enriched diet ,at the same time, group C was irrigated stomaches with losartan 25 mg·kg -1 ·d -1 and group D with captopril 12.5 mg·kg -1 ·d -1 . After 12 wk, blood samples were obtained for detection of serum lipids levels, plasma tissue type plasminogen activator (t PA) and plasminogen activator inhibitor (PAI 1) activities. Then all animals were killed and chests were opened to get the aortas. General specimens were made to estimate the atherosclerotic lesion. Ordinary pathological and electron microscope's sections were made to observe the histopathological changes of blood vessels, ultrastructure of intima. Rest aortic segments were made into homogenate for examination of the endothelin 1(ET 1) levels. RESULTS: Serum lipids and endothelin 1 levels of group B were significantly higher( P <0.01) than those of group A.
The aortic atherosclerotic lesions were more severe than those of group A, and plasma t PA activity was lower ( P <0.05) in atherosclerosis and PAI 1 activity was higher than that of Group A ( P <0.05). Through treatment with losartan or captopril, the serum lipids levels were not altered, but all area of atherosclerotic lesions, injury of endothelium, intima thickening reduced, and t PA activity and PAI 1 activity improved ( P <0.05) in group C or D. The differences between group C and group D were not significant ( P >0.05). Additionally, ET 1 levels decreased significantly after treatment with losartan( P <0.01) while those treated with captorpil did not. The injury of endothelium of group C and D was significantly milder than that of Group B. CONCLUSION:Both losartan and captopril have the beneficial effects of ameliorating the fibrinolytic function and reducing atherosclerotic lesion of cholesterol fed rabbits.