Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 52, Issue 7, Pages 1123-1134Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2011.12.028
Keywords
Acclimatization; Adaptation; Nitric oxide; Hypoxia; Altitude; Tibetan; Pulmonary artery pressure; High-altitude pulmonary edema; Free radicals
Funding
- NIH [HL60917]
- NSF [0924726, 0452326, 021547]
- Direct For Social, Behav & Economic Scie
- Division Of Behavioral and Cognitive Sci [0924726] Funding Source: National Science Foundation
- Division Of Behavioral and Cognitive Sci
- Direct For Social, Behav & Economic Scie [0452326] Funding Source: National Science Foundation
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This review summarizes published information on the levels of nitric oxide gas (NO) in the lungs and NO-derived liquid-phase molecules in the acclimatization of visitors newly arrived at altitudes of 2500 m or more and adaptation of populations whose ancestors arrived thousands of years ago. Studies of acutely exposed visitors to high altitude focus on the first 24-48 h with just a few extending to days or weeks. Among healthy visitors. NO levels in the lung, plasma, and/or red blood cells fell within 2 h, but then returned toward baseline or slightly higher by 48 h and increased above baseline by 5 days. Among visitors ill with high-altitude pulmonary edema at the time of the study or in the past, NO levels were lower than those of their healthy counterparts. As for highland populations, Tibetans had NO levels in the lung, plasma, and red blood cells that were at least double and in some cases orders of magnitude greater than other populations regardless of altitude. Red blood cell-associated nitrogen oxides were more than 200 times higher. Other highland populations had generally higher levels although not to the degree shown by Tibetans. Overall, responses of those acclimatized and those presumed to be adapted are in the same direction, although the Tibetans have much larger responses. Missing are long-term data on lowlanders at altitude showing how similar they become to the Tibetan phenotype. Also missing are data on Tibetans at low altitude to see the extent to which their phenotype is a response to the immediate environment or expressed constitutively. The mechanisms causing the visitors' and the Tibetans' high levels of NO and NO-derived molecules at altitude remain unknown. Limited data suggest processes including hypoxic upregulation of NO synthase gene expression, hemoglobin-NO reactions, and genetic variation. Gains in understanding will require integrating appropriate methods and measurement techniques with indicators of adaptive function under hypoxic stress. (C) 2012 Elsevier Inc. All rights reserved.
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