Cerebral vasodilatation to exogenous NO is a measure of fitness for life at altitude.
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.
Appenzeller
Otto
O
Department of Neurology, New Mexico Health Enhancement and Marathon Clinics (NMHEMC) Research Foundation, Albuquerque, NM 87122-1424, USA. oarun@unm.edu
Claydon
Victoria E
VE
Gulli
Giosué
G
Qualls
Clifford
C
Slessarev
Marat
M
Zenebe
Guta
G
Gebremedhin
Amha
A
Hainsworth
Roger
R
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
D020030:Nitric Oxide Donors; D002245:Carbon Dioxide; D009569:Nitric Oxide; D005996:Nitroglycerin; D007548:Isosorbide Dinitrate; D010100:Oxygen