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Background:Clarifying the mechanisms underlying vascular smooth muscle cell (VSMC) proliferation is important for the prevention and treatment of vascular remodeling and the reverse of hyperplastic lesions.Previous research has shown that the gaseous signaling molecule sulfur dioxide (SO2) inhibits VSMC proliferation,but the mechanism for the inhibition of the angiotensin Ⅱ (AngⅡ)-induced VSMC proliferation by SO2 has not been fully elucidated.This study was designed to investigate if SO2 inhibited VSMC proliferation in mice with hypertension induced by AngⅡ.Methods:Thirty-six male C57 mice were randomly divided into control,AngⅡ,and AngⅡ + SO2 groups.Mice in AngⅡ group and AngⅡ + SO2 group received a capsule-type AngⅡ pump implanted under the skin of the back at a slow-release dose of 1000 ng·kg-1 ·min-1.In addition,mice in AngⅡ + SO2 received intraperitoneal injections of SO2 donor.Arterial blood pressure of tail artery was determined.The thickness of the aorta was measured by elastic fiber staining,and proliferating cell nuclear antigen (PCNA) and phosphorylated-extracellular signal-regulated kinase (P-ERK) were detected in aortic tissues.The concentration of SO2 in serum and aortic tissue homogenate supematant was measured using high-performance liquid chromatography with fluorescence determination.In the in vitro study,VSMC of A7R5 cell lines was divided into six groups:control,AngⅡ,AngⅡ + SO2,PD98059 (an inhibitor of ERK phosphorylation),AngⅡ + PD98059,and AngⅡ + SO2 + PD98059.Expression of PCNA,ERK,and P-ERK was determined by West blotting.Results:In animal experiment,compared with the control group,AngⅡ markedly increased blood pressure (P ＜ 0.01) and thickened the aortic wall in mice (P ＜ 0.05) with an increase in the expression ofPCNA (P ＜ 0.05).SO2,however,reduced the systemic hypertension and the wall thickness induced by AngⅡ (P ＜ 0.05).It inhibited the increased expression of PCNA and P-ERK induced by AngⅡ (P ＜ 0.05).In cell experiment,PD98059,an ERK phosphorylation inhibitor,blocked the inhibitory effect of SO2 on VSMC proliferation (P ＜ 0.05).Conclusions:ERK signaling is involved in the mechanisms by which SO2 inhibits VSMC proliferation in AngⅡ-induced hypertensive mice via ERK signaling.