Membrane Rafts-redox Signaling Contribute To Endothelial Dysfunction And Vascular Remodeling Of Thoracic Aorta In Angiotensin Ⅱ-infused Rats

Membrane rafts(MRs)-redox pathway is characterized by NADPH oxidase activation via the clustering of its subunits through lysosome fusion and the activation of acid sphingomyelinase(ASMase).Our previous study shown that MRs-redox signaling pathway mediates angiontensin Ⅱ(AngⅡ)-induced production of reactive oxygen species(ROS)and endothelial dysfunction in rat mesenteric arteries.In the present study,we hypothesized that this signaling pathway is involved in blood pressure increase,endothelial dysfunction and vascular remodeling in AngⅡ-induced hypertensive animal model.Sixteen-week-old male Sprague Dawley rats were subjected to Ang Ⅱ infusion for two weeks with or without treatment with lysosome fusion inhibitor bafilomycin A1 and ASMase inhibitor amitriptyline.After treatments,aortas were harvested for further study.Results show that MRs-redox signaling pathway was activated as indicated by the increase of MRs formation,ASMase activity and ROS production in aorta from Ang Ⅱ-infused rats compared that from control rats.MRs formation and ROS production were significantly inhibited in thoracic aorta from Ang Ⅱ-induced rats treated with bafilomycin A1 and amitriptyline.Meanwhile,both treatments significantly attenuated blood pressure increase,endothelial dysfunction,vascular remodeling including medial hypertrophy,increased collagen and fibronectin deposition of thoracic aorta in thoracic aortas from Ang Ⅱinfused rats.Finally,both treatments significantly prevented the increase of inflammatory factors including monocyte chemotactic protein 1(MCP-1),intercellular adhesion molecule 1(ICAM-1)and tumor necrosis factor α(TNF-α)in thoracic aorta from Ang Ⅱ-infused rats.In conclusion,the present study demonstrates that MRs-redox signaling pathway was involved in endothelial dysfunction and medial remodeling in Ang Ⅱinduced hypertension.