Regulation effects of RAS antagonists on expression of proliferation and apoptosis factor in vascular smooth muscle cells

Objective To investigate the regulation effects of angiotensin converting enzyme inhibitor captopril and AT1 receptor antagonist losartan on expression of tumor necrosis factor-α(TNF-α)and transforming growth factor-β1(TGF-β1)induced by angiotensinⅡ(AngⅡ)in vascular smooth muscle cells.Methods Thoracic aortic vascular smooth muscle cells of male Wistar rats were cultured in vitro.The cultured cells were divided in to control group,AngⅡgroup,captopril group,losartan group,and captopril combined losartan group.Cells in all groups were collected at the culture end point.TNF-αand TGF-β1 mRNA expressions in the collected specimens were detected by reverse transcription-PCR(RTPCR)method,and the effects of AngⅡon TNF-αand TGF-β1 mRNA expression and the regulation of captopril and losartan were observed in different AngⅡconcentrations and different stimulating time in vascular smooth muscle cells.Results TNF-αmRNA expression increased with the increment of AngⅡconcentration and the action time(P<0.05 or P<0.01,except 10-8 mol/L).Captopril(5×10-6 mol/L)and losartan(5×10-6 mol/L)inhibited the action of AngⅡ(P<0.05).The most significant inhibition action occured when capopril combined with losartan(P<0.01).Inhibition effect of losartan on and TNF-αexpression occured later.TNF-αexpression was significantly decreased after 72 hours(P<0.05).TGF-β1 mRNA expression increased with the increment of concentration and the action time of AngⅡ(P<0.01);captopril and losartan decreased the expression of TGF-β1 mRNA(P<0.05 or P<0.01),especially when the two treatments were combined together.Conclusion AngⅡincreases the expressions of TNF-αand TGF-β1 mRNA expression in vascular smooth muscle cells,and the expressions increase with the AngⅡdose and action time.Captopril and losartan inhibit the TNF-α,TGF-β1 mRNA expressions of vascular smooth muscle cells induced by AngⅡ,and the inhibition is the strongest when losartan is combined with captopril.