Effects of losartan on the platelet activation and expression of angiotensin II AT_1 receptor mRNA after vascular balloon injury in rats

Objective: To investigate the process of neointimal formation,level of platelet activation,expression of angiotensinⅡ AT_1 receptor mRNA and effects of losartan on them after vascular balloon injury in rats.Methods: Forty-eight male Wister rats were randomly given aortic balloon injury by 2F balloon catheters(n=24),aortic balloon injury plus losartan(30?mg·kg~(-1)·d~(-1)) from 1 day before injury to 28 days after injury,and compared with the controls(n=24).The process of intimal thickening,number of platelet GMP-140 and level of AT_1 receptor mRNA were investigated at day 3,7,14 and 28 after injury by histological method,radioimmunological method and RT-PCR technique,respectively.Results: ① The expression of AT_1 receptor mRNA increased significantly at day 3 after balloon injury and remained high at day 14(P0.01).② The number of platelet GMP-140 was high at day 3 and began to decrease at day 7 after injury(P0.01).③ The migration and proliferation of vascular smooth muscle cells(VSMC) had existed at day 3 after balloon injury.The thickening of intima happened at day 7 after injury(P0.01) and acted more significant at day 14(P0.01).The proliferation of VSMC decreased at day 28,but extracellular matrix increased and intimal thickening continued(P0.01).④ In losartan treated group,the number of platelet GMP-140,proliferation of VSMC and intimal thickening reduced(P0.01),but the level of AT_1R mRNA increased(P0.01).Conclusion: The expression of AT_1R mRNA and the number of platelet GMP-140 increase in the process of intimal thickening after balloon injury.Losartan inhibits the activation of platelet and intimal thickening,but upregulates the expression of AT_1R mRNA.