University College, London. Centre for Altitude, Space and Extreme environment medicine. Caudwell Xtreme Everest Research Group (Including: Levett, Denny Z. H., Fernandez, Bernadette O., Riley, Heather L., Martin, Daniel S., Mitchell, Kay, Leckstrom, Carl A., Ince, C. (Can), Whipp, Brian J., Mythen, Monty, Montgomery, Hugh E., Grocott, Michael P. W. and Feelisch, Martin). (2011) The role of nitrogen oxides in human adaptation to hypoxia. Scientific Reports, Vol.1 (No.109). doi:10.1038/srep00109 ISSN 2045-2322.

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Abstract

Lowland residents adapt to the reduced oxygen availability at high altitude through a process known as acclimatisation, but the molecular changes underpinning these functional alterations are not well understood. Using an integrated biochemical/whole-body physiology approach we here show that plasma biomarkers of NO production (nitrite, nitrate) and activity (cGMP) are elevated on acclimatisation to high altitude while S-nitrosothiols are initially consumed, suggesting multiple nitrogen oxides contribute to improve hypoxia tolerance by enhancing NO availability. Unexpectedly, oxygen cost of exercise and mechanical efficiency remain unchanged with ascent while microvascular blood flow correlates inversely with nitrite. Our results suggest that NO is an integral part of the human physiological response to hypoxia. These findings may be of relevance not only to healthy subjects exposed to high altitude but also to patients in whom oxygen availability is limited through disease affecting the heart, lung or vasculature, and to the field of developmental biology.

Item Type:	Journal Article
Subjects:	Q Science > QP Physiology
Divisions:	Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Acclimatization -- Physiology, Nitrogen oxides -- Physiological effect, Altitude, Influence of
Journal or Publication Title:	Scientific Reports
Publisher:	Nature Publishing Group
ISSN:	2045-2322
Official Date:	6 October 2011
Dates:	Date Event 6 October 2011 Published
Volume:	Vol.1
Number:	No.109
DOI:	10.1038/srep00109
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access (Creative Commons)
Date of first compliant deposit:	19 December 2015
Date of first compliant Open Access:	19 December 2015
Funder:	BOC Health Care, Eli Lilly and Company, London Clinic, Smiths Medical, Montres Rolex S.A., Association of Anaesthetists of Great Britain and Ireland (AAGBI), Intensive Care Society (Great Britain) (ICS), Halley Stewart Trust, Great Britain. Dept. of Health (DoH), Medical Research Council (Great Britain) (MRC)

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