Cerebral Vasodilatation to Exogenous NO Is a Measure of Fitness for Life at Altitude

Abstract

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 (P ET CO 2 ), 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 CO 2 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. Key Words: altitude Ⅲ nitric oxide Ⅲ cerebral hypoxia Ⅲ cerebrovascular circulation Ⅲ evolution A ltitude is an inhospitable environment for humans, and yet permanent settlements are found at 5100 m. 1 The fall in barometric pressure with increasing altitude in these habitats reduces the availability of oxygen compared with sea level. Therefore, hypoxia in the mountains is inescapable. Ethiopian highlanders are, by some measures, the best adapted for life at altitude, 2 showing no evidence of chronic mountain sickness (CMS), a failure to adapt to altitude that is commonly seen in the high Andes. 3,4 The severity of CMS is inversely related to fitness for survival in the Andes.A key measure of survival in the mountains is the maintenance of optimal oxygen concentrations in all tissues. An adequate blood flow to the brain is essential for maintenance of a proper oxygen supply, and blood flow, in turn, is profoundly affected by changes in oxygen availability. In response to hypoxia, blood vessels, including those in the cerebral circulation, undergo NO-mediated vasodilatation. Inappropriate release of NO with hypoxia has been implicated in some maladaptation syndromes in sojourners to altitude. 5 We hypothesized that cerebrovascular responsiveness to NO donors would predict the ability for adaptation to life at high altitude. To test this proposal, we compared cerebral blood flow velocity (CBV) responses to NO donors in 2 populations: Peruvian native highlanders, who freq...

Cerebrovascular Responses to Hypoxia and Hypocapnia in Ethiopian High Altitude Dwellers

“…5,13 These findings confirm previous suggestions that the Ethiopian pattern of adaptation to altitude may be beneficial for high altitude living. 9 …”

“…13 Our data are consistent with the lack of evidence of CMS based on hemoglobin levels and SaO 2 reported in earlier population-based studies from the Ethiopian highlands, 11 and suggests that Ethiopians are better adapted for high altitude living. 9 …”

“…The higher SaO 2 and P ET o 2 in Ethiopians support the suggestion that they show enhanced adaptation to high altitude living. 9 Respiratory adaptation patterns are discussed below.…”

“…8 It has emerged recently that Ethiopian altitude dwellers may use different adaptive strategies to hypoxia. 9,10 Ethiopians living on high plateaux have lower hemoglobin levels and hence presumably lower hematocrits than Peruvians, 1,11 and there are no reports of CMS in Ethiopians. The adaptations of Ethiopians may be more beneficial for high altitude living, 9 which could explain the apparent absence of CMS in Ethiopia.…”

“…Furthermore, we also showed that cerebrovascular responses to exogenous nitric oxide (NO, the proposed mediator of hypoxic vasodilatation) are different between Ethiopians and Peruvians, and may be related to fitness for life at high altitudes. 9 However, the responses of the cerebral circulation to physiological changes in end-tidal oxygen (P ET o 2 ) and carbon dioxide (P ET co 2 ) in Ethiopian high altitude dwellers are unknown. The aim of this study, therefore, was to examine the cerebrovascular responses to changes in P ET o 2 and P ET co 2 in Ethiopian high altitude dwellers, and to compare them with those previously obtained 13 in HA and CMS Peruvians.…”