PMID- 30924217 OWN - NLM STAT- MEDLINE DCOM- 20200724 LR - 20200724 IS - 1469-445X (Electronic) IS - 0958-0670 (Linking) VI - 104 IP - 6 DP - 2019 Jun TI - Membrane raft redox signalling contributes to endothelial dysfunction and vascular remodelling of thoracic aorta in angiotensin II-infused rats. PG - 946-956 LID - 10.1113/EP087335 [doi] AB - NEW FINDINGS: What is the central question of this study? Is the membrane raft redox signalling pathway involved in blood pressure increase, endothelial dysfunction and vascular remodelling in an angiotensin II-induced hypertensive animal model? What is the main finding and its importance? The membrane raft redox signalling pathway was involved in endothelial dysfunction and medial remodelling in angiotensin II-induced hypertension. ABSTRACT: The membrane raft (MR) 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 shows that the MR redox signalling pathway is associated with 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 signalling pathway is involved in blood pressure increase, endothelial dysfunction and vascular remodelling in an AngII-induced hypertensive animal model. Sixteen-week-old male Sprague-Dawley rats were subjected to AngII infusion for 2 weeks with or without treatment with the lysosome fusion inhibitor bafilomycin A1 and ASMase inhibitor amitriptyline. After treatments, aortas were harvested for further study. The results showed that the MR redox signalling pathway was activated as indicated by the increase of MR formation, ASMase activity and ROS production in aorta from AngII-infused rats compared with that from control rats. MR formation and ROS production were significantly inhibited in thoracic aorta from AngII-induced rats treated with bafilomycin A1 and amitriptyline. Both treatments significantly attenuated blood pressure increase, endothelial dysfunction and vascular remodelling including medial hypertrophy, and increased collagen and fibronectin deposition in thoracic aortas from AngII-infused rats. Finally, both treatments significantly prevented the increase of inflammatory factors including monocyte chemotactic protein 1, intercellular adhesion molecule 1 and tumour necrosis factor alpha in thoracic aorta from AngII-infused rats. In conclusion, the present study demonstrates that the MR redox signalling pathway was involved in endothelial dysfunction and medial remodelling in AngII-induced hypertension. CI - (c) 2019 The Authors. Experimental Physiology (c) 2019 The Physiological Society. FAU - Wei, Jian AU - Wei J AD - Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. AD - Shanghai Institute of Hypertension, Shanghai, China. FAU - Xu, Lian AU - Xu L AD - Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. AD - Shanghai Institute of Hypertension, Shanghai, China. FAU - Du, Ya-Nan AU - Du YN AD - Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. AD - Shanghai Institute of Hypertension, Shanghai, China. FAU - Tang, Xiao-Feng AU - Tang XF AD - Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. AD - Shanghai Institute of Hypertension, Shanghai, China. FAU - Ye, Mao-Qing AU - Ye MQ AD - Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. AD - Shanghai Institute of Hypertension, Shanghai, China. FAU - Wu, Yong-Jie AU - Wu YJ AD - Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. AD - Shanghai Institute of Hypertension, Shanghai, China. FAU - Han, Wei-Qing AU - Han WQ AUID- ORCID: 0000-0001-9702-0523 AD - Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. AD - Shanghai Institute of Hypertension, Shanghai, China. AD - Laboratory of Vascular Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China. FAU - Gao, Ping-Jin AU - Gao PJ AD - Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. AD - Shanghai Institute of Hypertension, Shanghai, China. AD - Laboratory of Vascular Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China. LA - eng GR - 81100184/National Natural Science Foundation of China/International GR - 81230071/National Natural Science Foundation of China/International GR - 81570221/National Natural Science Foundation of China/International GR - 91539202/National Natural Science Foundation of China/International GR - 81200203/National Natural Science Foundation of China/International GR - 81300089/National Natural Science Foundation of China/International GR - 17ZR1423700/Shanghai Nature Science Foundation/International GR - 14PJ1406400/Pujiang Program of the Shanghai Science and Technology Committee/International GR - 201540037/Shanghai Medical Bureau Fund/International GR - 14XJ10042/Scientific Fund of Shanghai Jiao Tong University School of Medicine/International GR - Scientific Research Foundation for the Returned Overseas Chinese Scholars of the State Education Ministry/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190501 PL - England TA - Exp Physiol JT - Experimental physiology JID - 9002940 RN - 0 (Reactive Oxygen Species) RN - 11128-99-7 (Angiotensin II) SB - IM MH - Angiotensin II MH - Animals MH - Aorta, Thoracic/*metabolism MH - Blood Pressure/physiology MH - Endothelium, Vascular/*metabolism MH - Hypertension/chemically induced/*metabolism MH - Male MH - Membrane Microdomains/*metabolism MH - Oxidation-Reduction MH - Rats MH - Rats, Sprague-Dawley MH - Reactive Oxygen Species/*metabolism MH - Signal Transduction/physiology MH - Vascular Remodeling/*physiology OTO - NOTNLM OT - angiotensin II OT - endothelial dysfunction OT - hypertension OT - membrane rafts OT - vascular remodelling EDAT- 2019/03/30 06:00 MHDA- 2020/07/25 06:00 CRDT- 2019/03/30 06:00 PHST- 2018/08/27 00:00 [received] PHST- 2019/03/12 00:00 [accepted] PHST- 2019/03/30 06:00 [pubmed] PHST- 2020/07/25 06:00 [medline] PHST- 2019/03/30 06:00 [entrez] AID - 10.1113/EP087335 [doi] PST - ppublish SO - Exp Physiol. 2019 Jun;104(6):946-956. doi: 10.1113/EP087335. Epub 2019 May 1.