title: ERK signaling mediates enhanced angiotensin II-induced rat aortic constriction following chronic intermittent hypoxia.
abstract: BACKGROUND
  Obstructive sleep apnea (OSA) has been recognized as an independent risk factor for systemic hypertension. The study investigated the functional consequences of chronic intermittent hypoxia (CIH) on aortic constriction induced by angiotensin II (Ang II) and the possible signaling involving ERK1/2 and contractile proteins such as myosin light chain kinase (MLCK), myosin phosphatase targeting subunit (MYPT1) and myosin light chain (MLC).
  
  
  METHODS
  Male Wistar rats were randomly divided into CIH group and normoxia group and exposed to either CIH procedure or air-air cycles. Phosphorylation of ERK1/2, MYPT1 and MLC was assessed by Western blotting following constrictor studies in the presence or absence of PD98059 (10 µmol/L).
  
  
  RESULTS
  CIH-exposure resulted in more body weight gain and elevated blood pressure, which could be attenuated by pretreatment with PD98059. Endothelium-removed aortic rings from CIH rats exhibited higher constrictor sensitivity to Ang II (Emax: (138.56 ± 5.78)% versus (98.45±5.31)% of KCl; pD2: 7.98 ± 0.14 versus 8.14 ± 0.05, respectively). CIH procedure exerted complex effects on ERK expressions (total ERK1/2 decreased whereas the ratio of phosphorylated to total ERK1/2 increased). CIH aortas had higher MLCK mRNA and basal phosphorylation of MYPT1 and MLC. In parallel to greater increases in phosphorylation of ERK1/2, MYPT1 and MLC, Ang II-induced aortic constriction was significantly enhanced in CIH rats, which was largely reversed by PD98059. However vascular constriction of normoxia rats remained unchanged despite similar but smaller changing tendency of proteins phosphorylation.
  
  
  CONCLUSIONS
  These data suggest that CIH exposure results in aortic hyperresponsiveness to Ang II, presumably owing to more activated ERK1/2 signaling pathway.
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, Key Laboratory of Respiratory Disease of the Ministry of Health, Wuhan, Hubei 430030, China.
authors.forename: Xue-Ling
authors.initials: XL
authors.lastname: Guo
authors.forename: Yan
authors.initials: Y
authors.lastname: Deng
authors.forename: Jin
authors.initials: J
authors.lastname: Shang
authors.forename: Kui
authors.initials: K
authors.lastname: Liu
authors.forename: Yong-Jian
authors.initials: YJ
authors.lastname: Xu
authors.forename: Hui-Guo
authors.initials: HG
authors.lastname: Liu
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects*; D005419:Flavonoids / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D005419:Flavonoids; D000804:Angiotensin II; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one