title: Arterial hypertension in a murine model of sleep apnea: role of NADPH oxidase 2.
abstract: OBJECTIVE
  To investigate whether NADPH oxidase 2 (NOX2), a major source of reactive oxygen species (ROS), contributes to the emergence of arterial hypertension in a murine model of sleep apnea.
  
  
  BACKGROUND
  Obstructive sleep apnea (OSA) is a risk factor for arterial hypertension and it is linked to oxidative stress.
  
  
  METHODS
  C57BL/6J mice were exposed to chronic intermittent hypoxia (CIH) for 6 weeks (5 days/week, 8 h/day, alternating cycles of hypoxia and normoxia, each lasting 120 s, nadir FiO2: 7%). Blood pressure was monitored by telemetric catheters implanted into the abdominal aorta. Pharmacological inhibition of NOX by apocynin and NOX2-deficient mice were used to assess the role of NOX in CIH-induced arterial hypertension. NOX2 gene expression was measured by real-time PCR in different cardiovascular tissues.
  
  
  RESULTS
  When compared with room air conditions, wild-type mice showed significant blood pressure elevations after exposure to CIH. This response was attenuated after treating animals with apocynin and in NOX2 (=gp91) knockout mice, whereas NOX2 was not upregulated in the heart, aorta, and femoral/carotid arteries of CIH mice.
  
  
  CONCLUSIONS
  We suggest that the CIH-induced arterial hypertension is mediated by ROS derived from an activation of NOX2 within cells located outside the cardiovascular system.
authors.affiliation: aUniversities of Giessen and Marburg Lung Center, Excellence Cluster Cardio-Pulmonary System, German Lung Research Center, Justus-Liebig-University Giessen, Giessen bDepartment of Internal Medicine, Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Berlin cDepartment of Lung Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany.
authors.forename: Richard
authors.initials: R
authors.lastname: Schulz
authors.forename: Gulsina
authors.initials: G
authors.lastname: Murzabekova
authors.forename: Bakytbek
authors.initials: B
authors.lastname: Egemnazarov
authors.forename: Simone
authors.initials: S
authors.lastname: Kraut
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Eisele
authors.forename: Rio
authors.initials: R
authors.lastname: Dumitrascu
authors.forename: Jörg
authors.initials: J
authors.lastname: Heitmann
authors.forename: Michael
authors.initials: M
authors.lastname: Seimetz
authors.forename: Martin
authors.initials: M
authors.lastname: Witzenrath
authors.forename: Hossein A
authors.initials: HA
authors.lastname: Ghofrani
authors.forename: Ralph T
authors.initials: RT
authors.lastname: Schermuly
authors.forename: Friedrich
authors.initials: F
authors.lastname: Grimminger
authors.forename: Werner
authors.initials: W
authors.lastname: Seeger
authors.forename: Norbert
authors.initials: N
authors.lastname: Weissmann
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000201:enzymology* / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012307:Risk Factors; D020181:Sleep Apnea, Obstructive / Q000150:complications* / Q000201:enzymology*
chemical_list: D000098:Acetophenones; D004791:Enzyme Inhibitors; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C056165:acetovanillone; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases