Inhibition effect of captopril and losartan on expression of matrix metalloproteinase-1,-9 induced by angiotensin Ⅱ in rat vascular smooth muscle cells

Objective To investigate the effect of angiotensin converting enzyme inhibitor (ACEI) captopril and angiotensin Ⅱ receptor antagonist losartan on the mRNA expression of matrix metalloproteinase (MMP)-1 and MMP-9 in vascular smooth muscle cells induced by angiotensin Ⅱ (Ang Ⅱ ).Methods Male Wistar rats' thoracic aortic vascular smooth muscle cells were cultured in vitro.The cultured cells were divided in to control group,Ang Ⅱ group,captopril group,losartan group,and captopril plus losartan group.Cells in all groups were collected at the culture end-point.MMP-1 and MMP-9 mRNA expressions were detected by RT-PCR method in the collected specimens,and the effects of Ang Ⅱ on MMP-1 and MMP-9 mRNA expression and the intervention effects of captopril and losartan were observed in different Ang Ⅱ concentrations and different action times to vascular smooth muscle cells.Results ( 1 ) MMP-1 mRNA expression gradually increased along with the increments of Ang Ⅱ concentration and the action time (P＜0.05),and the most significant concentration was 10-6 mol/L (P＜0.01).(2)Captopril (5 × 10-6 mol/L) and losartan (5 × 10-6mol/L) inhibited the action of AngⅡ (P＜0.05,P＜0.01).MMP-9 mRNA expression was 0.47±0.03 ,0.86 ± 0.04,0.94±0.14 and 1.12±0.19 vs.0.10±0.04 (P＜0.05,P＜0.01) respectively when Ang Ⅱ concentration was 10-7 ,10-6 ,10-5 and 10-4 mol/L respectively.Captopril (5 × 10-6mol/L) and losartan (5 × 10-6 mol/I) significantly inhibited the MMP-9 mRNA expression which was stimulated by Ang Ⅱ (P＜0.05,P＜0.01),especially in captopril plus losartan group.The MMP-9 mRNA expression increased with the prolonging of stimulating time of Ang Ⅱ,MMP-9 mRNA expression was earlier than that of MMP-1.Conclusions AngⅡ increases the expression of MMP-1 and MMP-9 of vascular smooth muscle cells in a dose-and time-dependence manner.Captopril and losartan inhibit the MMP-1 and MMP-9 mRNA expression of vascular smooth muscle cells induced by Ang Ⅱ ,and the inhibition is the strongest when losartan was combined with captopril.The inhibitive effects is positively correlated to action time.