title: Cerebral vasodilatation to exogenous NO is a measure of fitness for life at altitude.
abstract: OBJECTIVE
  Andean highlanders, unlike Ethiopians, develop chronic mountain sickness (CMS), a maladaptation to their native land. Ambient hypoxia induces NO-mediated vasodilatation. Fitness for life at altitude might be revealed by cerebrovascular responses to NO.
  
  
  METHODS
  Nine altitude-native men were examined at 3622 and 794 m in Ethiopia and compared with 9 altitude-native Andean men tested at 4338 and 150 m in Peru. We assessed CMS scores, hematocrits, end-tidal pressure of carbon dioxide (P(ET)co2), oxygen saturations, and cerebral blood flow velocity (CBV). We evaluated fitness for life at altitude from the cerebrovascular response to an exogenous NO donor.
  
  
  RESULTS
  At high altitude, CMS scores and hematocrits were higher in Andeans, and they had lower oxygen saturations. Ethiopians had higher P(ET)co2 at all study sites. At low altitude, saturations were similar in both groups. Responsiveness of the cerebral circulation to NO was minimal in Ethiopians at low altitude, whereas Andeans had a large response. In contrast, at high altitude, Ethiopians showed large responses, and Peruvians had minimal responses.
  
  
  CONCLUSIONS
  By our measure, high altitude-native Peruvians were well-adapted lowlanders, whereas Ethiopian highlanders were well adapted to altitude life. Environmental pressures were sufficient for human adaptation to chronic hypoxia in Africa but not South America. The mechanisms underlying these differences are unknown, although studies of neurovascular diseases suggest that this may be related to a NO receptor polymorphism.
authors.affiliation: Department of Neurology, New Mexico Health Enhancement and Marathon Clinics (NMHEMC) Research Foundation, Albuquerque, NM 87122-1424, USA. oarun@unm.edu
authors.forename: Otto
authors.initials: O
authors.lastname: Appenzeller
authors.forename: Victoria E
authors.initials: VE
authors.lastname: Claydon
authors.forename: Giosué
authors.initials: G
authors.lastname: Gulli
authors.forename: Clifford
authors.initials: C
authors.lastname: Qualls
authors.forename: Marat
authors.initials: M
authors.lastname: Slessarev
authors.forename: Guta
authors.initials: G
authors.lastname: Zenebe
authors.forename: Amha
authors.initials: A
authors.lastname: Gebremedhin
authors.forename: Roger
authors.initials: R
authors.lastname: Hainsworth
mesh_terms: D000064:Acclimatization / Q000502:physiology*; D000328:Adult; D000532:Altitude Sickness / Q000453:epidemiology / Q000208:ethnology / Q000503:physiopathology*; D044383:Black People / Q000235:genetics; D001783:Blood Flow Velocity; D001944:Breath Tests; D002245:Carbon Dioxide / Q000032:analysis; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D005002:Ethiopia / Q000453:epidemiology; D006400:Hematocrit; D006801:Humans; D002534:Hypoxia, Brain / Q000208:ethnology / Q000209:etiology / Q000503:physiopathology*; D007199:Indians, South American / Q000235:genetics; D007548:Isosorbide Dinitrate / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D010100:Oxygen / Q000097:blood; D010568:Peru / Q000453:epidemiology / Q000208:ethnology; D010809:Physical Fitness; D012641:Selection, Genetic
chemical_list: D020030:Nitric Oxide Donors; D002245:Carbon Dioxide; D009569:Nitric Oxide; D005996:Nitroglycerin; D007548:Isosorbide Dinitrate; D010100:Oxygen