title: Oxidative-nitrosative stress and systemic vascular function in highlanders with and without exaggerated hypoxemia.
abstract: BACKGROUND
  Acute exposure to high altitude stimulates free radical formation in lowlanders, yet whether this persists during chronic exposure in healthy, well-adapted and maladapted highlanders suffering from chronic mountain sickness (CMS) remains to be established.
  
  
  METHODS
  Oxidative-nitrosative stress (as determined by the presence of the biomarkers ascorbate radical [A •- ], via electron paramagnetic resonance spectroscopy, and nitrite [NO 2 2 ], via ozone-based chemiluminescence) was assessed in venous blood of 25 male highlanders in Bolivia living at 3,600 m with CMS (n 5 13, CMS 1 ) and without CMS (n 5 12, CMS 2 ). Twelve age- and activity-matched, healthy, male lowlanders were examined at sea level and during acute hypoxia. We also measured fl ow-mediated dilatation (FMD), arterial stiffness defined by augmentation index normalized for a heart rate of 75 beats/min (AIx-75), and carotid intima-media thickness (IMT).
  
  
  RESULTS
  Compared with normoxic lowlanders, oxidative-nitrosative stress was moderately increased in the CMS 2 group ( P , .05), as indicated by elevated A •- (3,191 457 arbitrary units [AU] vs 2,640 445 AU) and lower NO 2 2 (206 55 nM vs 420 128 nM), whereas vascular function remained preserved. This was comparable to that observed during acute hypoxia in lowlanders in whom vascular dysfunction is typically observed. In contrast, this response was markedly exaggerated in CMS 1 group (A •- , 3,765 429 AU; NO 2 2 , 148 50 nM) compared with both the CMS 2 group and lowlanders ( P , .05). This was associated with systemic vascular dysfunction as indicated by lower ( P , .05 vs CMS 2 ) FMD (4.2% 0.7% vs 7.6% 1.7%) and increased AIx-75 (23% 8% vs 12% 7%) and carotid IMT (714 127 m M vs 588 94 m M).
  
  
  CONCLUSIONS
  Healthy highlanders display a moderate, sustained elevation in oxidative-nitrosative stress that, unlike the equivalent increase evoked by acute hypoxia in healthy lowlanders, failed to affect vascular function. Its more marked elevation in patients with CMS may contribute to systemic vascular dysfunction.
authors.affiliation: Neurovascular Research Laboratory, Faculty of Health, Science and Sport, University of Glamorgan, Wales; Sondes Moléculaires en Biologie et Stress Oxydant, Institut de Chimie Radicalaire, Centre National de la Recherche Scientifique UMR 7273, Aix-Marseille University, France. Electronic address: dbailey1@glam.ac.uk.
authors.forename: Damian M
authors.initials: DM
authors.lastname: Bailey
authors.affiliation: Department of Cardiology, University Hospital of Bern, Bern, Switzerland.
authors.forename: Stefano F
authors.initials: SF
authors.lastname: Rimoldi
authors.affiliation: Department of Cardiology, University Hospital of Bern, Bern, Switzerland.
authors.forename: Emrush
authors.initials: E
authors.lastname: Rexhaj
authors.affiliation: Institute of Clinical Physiology, CNR, Pisa, Italy.
authors.forename: Lorenza
authors.initials: L
authors.lastname: Pratali
authors.affiliation: Instituto Boliviano de Biologia de Altura, La Paz, Bolivia.
authors.forename: Carlos
authors.initials: C
authors.lastname: Salinas Salmòn
authors.affiliation: Instituto Boliviano de Biologia de Altura, La Paz, Bolivia.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Villena
authors.affiliation: Centre for Clinical and Population Sciences, Queen's University Belfast, Belfast, Northern Ireland.
authors.forename: Jane
authors.initials: J
authors.lastname: McEneny
authors.affiliation: Centre for Clinical and Population Sciences, Queen's University Belfast, Belfast, Northern Ireland.
authors.forename: Ian S
authors.initials: IS
authors.lastname: Young
authors.affiliation: Botnar Center for Clinical Research, Hirslanden Group, Lausanne, Switzerland.
authors.forename: Pascal
authors.initials: P
authors.lastname: Nicod
authors.affiliation: Department of Cardiology, University Hospital of Bern, Bern, Switzerland.
authors.forename: Yves
authors.initials: Y
authors.lastname: Allemann
authors.affiliation: Department of Cardiology, University Hospital of Bern, Bern, Switzerland; Botnar Center for Clinical Research, Hirslanden Group, Lausanne, Switzerland; Facultad de Ciencias, Departamento de Biología, Universidad de Tarapacá, Arica, Chile.
authors.forename: Urs
authors.initials: U
authors.lastname: Scherrer
authors.affiliation: Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Claudio
authors.initials: C
authors.lastname: Sartori
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology; D000531:Altitude; D000532:Altitude Sickness / Q000378:metabolism / Q000503:physiopathology*; D000975:Antioxidants / Q000378:metabolism; D001838:Bolivia; D002319:Cardiovascular System / Q000503:physiopathology*; D059168:Carotid Intima-Media Thickness; D016022:Case-Control Studies; D005609:Free Radicals / Q000378:metabolism; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D015538:Nitrosation / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology*
chemical_list: D000975:Antioxidants; D005609:Free Radicals; D009569:Nitric Oxide