title: Losartan attenuates aortic endothelial apoptosis induced by chronic intermittent hypoxia partly via the phospholipase C pathway.
abstract: OBJECTIVE
  Endoplasmic reticulum (ER) stress is known to play key roles in the development of endothelial cell apoptosis induced by chronic intermittent hypoxia (CIH), and the angiotensin II-phospholipase C-inositol-1,4,5-triphosphate (AngII-PLC-IP3) pathway has been demonstrated to induce ER stress. To explore whether the AngII-PLC-IP3 pathway is involved in the vascular damage induced by CIH, we examined whether the AngII-PLC-IP3 pathway is involved in ER stress induced by CIH and whether losartan, a selective angiotensin II type 1 receptor (AT1R) blocker, could suppress endothelial cell apoptosis induced by CIH.
  
  
  METHODS
  Adult male Sprague Dawley rats were subjected to 8 h/day of intermittent hypoxia/normoxia, with or without losartan, a selective AT1R blocker, and/or U73122, a selective PLC inhibitor, for 8 weeks. Endothelial cell apoptosis, ER stress markers, and levels of PLC-γ1 and IP3R expression were determined.
  
  
  RESULTS
  Losartan prevented increases in PLC-γ1 and IP3R protein levels and inhibited ER stress markers induced by CIH. Addition of U73122 reproduced all the protective effects of losartan. Losartan administration before CIH significantly ameliorated CIH-induced endothelial cell apoptosis.
  
  
  CONCLUSIONS
  This study showed that the AngII-PLC-IP3 pathway is involved in ER stress induced by CIH and that pre-losartan administration ameliorates endothelial cell apoptosis following CIH partly via inhibition of the AngII-PLC-IP3 pathway and ER stress.
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, No. 1095 Jiefang Road, Wuhan, 430030, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ren
authors.affiliation: The Third Hospital Affiliated to Kunming Medical University, No. 174 People's West Road, Kunming, 650106, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, No. 1095 Jiefang Road, Wuhan, 430030, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, No. 1095 Jiefang Road, Wuhan, 430030, China.
authors.forename: Guang-Cai
authors.initials: GC
authors.lastname: Li
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, No. 1095 Jiefang Road, Wuhan, 430030, China.
authors.forename: Yue-Ying
authors.initials: YY
authors.lastname: Pan
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, No. 1095 Jiefang Road, Wuhan, 430030, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Xie
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, No. 1095 Jiefang Road, Wuhan, 430030, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Jin
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, No. 1095 Jiefang Road, Wuhan, 430030, China. hgliu@tjh.tjmu.edu.cn.
authors.forename: Hui-Guo
authors.initials: HG
authors.lastname: Liu
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology*; D017209:Apoptosis / Q000187:drug effects*; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D000860:Hypoxia / Q000150:complications*; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D010738:Type C Phospholipases / Q000378:metabolism*
chemical_list: D010738:Type C Phospholipases; D019808:Losartan
keywords: Chronic intermittent hypoxia; ER stress; Endothelial cell apoptosis; Losartan; PLC-IP3 pathway