Published Online
on June 8, 2006

A more recent version of this article appeared on July 1, 2006

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Submitted on January 9, 2006
Revised on February 13, 2006
Accepted on March 9, 2006

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

Otto Appenzeller MD^*; Victoria E. Claydon PhD; Giosué Gulli MD; Clifford Qualls PhD; Marat Slessarev BSc; Guta Zenebe MD; Amha Gebremedhin MD; and Roger Hainsworth MD

From the Department of Neurology (O.A.), New Mexico Health Enhancement and Marathon Clinics (NMHEMC) Research Foundation, Albuquerque, NM; International Collaboration On Repair Discoveries (V.E.C.), University of British Columbia, Vancouver, BC, Canada; Institute for Cardiovascular Research (G.G., R.H.), University of Leeds, United Kingdom; Department of Mathematics and Statistics (C.Q.), University of New Mexico, Albuquerque, NM; Department of Anesthesiology (M.S.), University of Toronto, Canada; Department of Neurology (G.Z.), Yehuleshet Higher Clinic, and Department of Medicine (A.G.), University of Addis Ababa, Ethiopia.

^* To whom correspondence should be addressed. E-mail: oarun{at}unm.edu.

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_ETCO₂), 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_ETCO₂ 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 • nitric oxide • cerebral hypoxia • cerebrovascular circulation • evolution

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