SPH3127 Improves Vascular Remodeling in Hypertensive Rats Through ERK1/2-Cx43 Signaling Pathway
Objective To investigate whether the renin inhibitor SPH3127 attenuates vascular remodeling to achieve antihypertensive and target organ protective effects through inhibiting the ERK1/2/Cx43 signaling pathway as well as the blocking effect of SPH3127 on the RAAS cascade response.Methods Seventy-five healthy male SD rats were divided into sham operation group,hypertension model group,SPH3127group,valsartan group and glyburide(Cx43 inhibitor)group.Systolic blood pressure(SBP)was measured,serum and thoracic aorta tissues were collected.Angiotensin Ⅱ(Ang Ⅱ)level was detected by enzyme-linked immunosorbent assay(ELISA),morphological changes of thoracic aorta were observed by hematoxylin-eosin staining,wall thickness(WT),internal diameter(ID),wall thickness/internal diameter(W/I),wall-lumen ratio(WLR)were measured;Extracellular regulated pretein kinase1/2(ERK1/2),Connexin 43(Cx43),α-smooth mouscle actin(α-SMA),proliferating cell nuclear antigen(PCNA),osteopontin(OPN)protein ex-pression was detected by Western blot.Results Compared with the sham operation group,SBP and Ang Ⅱ levels were increased in the hypertension model group,WT,ID,W/I and WLR were enlarged,the expression levels of PCNA,OPN,ERK1/2 and Cx43 were in-creased,and the expression level of α-SMA was decreased(P＜0.05);compared with the hypertension model group,SBP and Ang Ⅱ levels were decreased in the SPH3127group,and WT,ID,W/I,WLR were decreased,PCNA,OPN,ERK1/2,Cx43 expression levels were decreased,and α-SMA expression level was increased(P＜0.05);the expression level of Ang Ⅱ in SPH3127group was lower than that in valsartan group(P＜0.05).Conclusion SPH3127 can play a role in decreasing blood pressure and improving vascular remode-ling by blocking the RAAS cascade reaction through the inhibition of Ang Ⅱ production,the mechanism of which is related to its inhibition of ERK1/2/Cx43signaling pathway after the reduction in the expression levels of PCNA,OPN,and the increase in the expression level of α-SMA.
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