BACKGROUND AND PURPOSE-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(PETco2),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 PETco2 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.hypoxia induces NO-m ediated vasod life at altitude might be revealed b sponses to NO.M ETH OD S-N ine alt exam ined at 3622and 794m in E with 9altitude-native A ndean m en te BACKGROUND AND PURPOSE-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 have CMS scores, hematocrits, end-tidal pressure of carbon dioxide (PETco2), oxygen saturations, and cerebral blood flow velocity (CBV) .We like 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 PETco2 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, while 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, but Ethiopian highlanders were well adapted to altitude life. Environmental stress 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.hypoxia induces NO-m ediated vasod life at altitude might be revealed b sponses to NO.M ETH OD SN ine alt examined at 3622and 794m in E with 9altitude-native A ndean m en te