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Endogenous Urate Production Augments Plasma Antioxidant Capacity in Healthy Lowland Subjects Exposed to High Altitude^*

^* From Apex (altitude physiology expeditions) [Drs. Baillie, Bates, Thompson, Partridge, Schnopp, and Simpson], College of Medicine & Veterinary Medicine; and Clinical Pharmacology Unit (Drs. Waring, Maxwell, and Webb, and Ms. Gulliver-Sloan), Centre for Cardiovascular Science, University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh, UK.

Correspondence to: J. Kenneth Baillie, BSc, MBChB, MRCP, Apex (altitude physiology expeditions), c/o College of Medicine & Veterinary Medicine, University of Edinburgh, The Queen’s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK; e-mail: j.k.baillie{at}doctors.org.uk

Abstract

Background: Both tissue hypoxia in vitro, and whole-body hypoxia in vivo, have been found to promote the release of reactive oxygen species (ROS) that are potentially damaging to the cardiovascular system. Antioxidant systems protect against oxidative damage by ROS and may exhibit some degree of responsiveness to oxidative stimuli. Production of urate, a potent soluble antioxidant, is increased in hypoxic conditions. We aimed to determine whether urate is an important antioxidant defense in healthy subjects exposed to hypoxia.

Methods: We conducted a cohort study of 25 healthy lowland volunteers during acute exposure to high altitude (4 days at 3,600 m, followed by 10 days at 5,200 m) on the Apex high-altitude research expedition to Bolivia. We measured markers of oxidative stress (8-isoprostane F2), serum urate concentration, and total plasma antioxidant activity by two techniques: 2,2'-amino-di-[3-ethylbenzthiazole sulfonate] spectrophotometry (total antioxidant status [TAS]) and enhanced chemiluminescence (ECL).

Results: On ascent, F2-isoprostane levels were significantly elevated compared with those at sea level (p < 0.01). After 1 week at high altitude, plasma antioxidant capacity (AOC) by both TAS and ECL, and serum urate concentration were significantly elevated (each p < 0.01 vs sea level), and F2-isoprostane levels were reduced to values at sea level. There was a highly significant correlation between plasma urate and AOC at this stage (ECL, r² = 0.59, p = 0.0001; TAS, r² = 0.30, p = 0.0062).

Conclusions: Our results support the hypothesis that urate may act as a responsive endogenous antioxidant in high-altitude hypoxia.

Key Words: altitude • free radicals • hypoxia • oxidative stress • uric acid