title: Systemic oxidative-nitrosative-inflammatory stress during acute exercise in hypoxia; implications for microvascular oxygenation and aerobic capacity.
abstract: Exercise performance in hypoxia may be limited by a critical reduction in cerebral and skeletal tissue oxygenation, although the underlying mechanisms remain unclear. We examined whether increased systemic free radical accumulation during hypoxia would be associated with elevated microvascular deoxygenation and reduced maximal aerobic capacity (V̇O2 max ). Eleven healthy men were randomly assigned single-blind to an incremental semi-recumbent cycling test to determine V̇O2 max in both normoxia (21% O2) and hypoxia (12% O2) separated by a week. Continuous-wave near-infrared spectroscopy was employed to monitor concentration changes in oxy- and deoxyhaemoglobin in the left vastus lateralis muscle and frontal cerebral cortex. Antecubital venous blood samples were obtained at rest and at V̇O2 max to determine oxidative (ascorbate radical by electron paramagnetic resonance spectroscopy), nitrosative (nitric oxide metabolites by ozone-based chemiluminescence and 3-nitrotyrosine by enzyme-linked immunosorbent assay) and inflammatory stress biomarkers (soluble intercellular/vascular cell adhesion 1 molecules by enzyme-linked immunosorbent assay). Hypoxia was associated with increased cerebral and muscle tissue deoxygenation and lower V̇O2 max (P < 0.05 versus normoxia). Despite an exercise-induced increase in oxidative-nitrosative-inflammatory stress, hypoxia per se did not have an additive effect (P > 0.05 versus normoxia). Consequently, we failed to observe correlations between any metabolic, haemodynamic and cardiorespiratory parameters (P > 0.05). Collectively, these findings suggest that altered free radical metabolism cannot explain the elevated microvascular deoxygenation and corresponding lower V̇O2 max in hypoxia. Further research is required to determine whether free radicals when present in excess do indeed contribute to the premature termination of exercise in hypoxia.
authors.affiliation: Vascular Physiology Unit, Institute of Cardiovascular Science, University College London, London, UK.
authors.forename: John D S
authors.initials: JD
authors.lastname: Woodside
authors.affiliation: Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Gutowski
authors.affiliation: Neurovascular Research Laboratory, Faculty of Life Sciences and Education, University of South Wales, Pontypridd, UK.
authors.forename: Lewis
authors.initials: L
authors.lastname: Fall
authors.affiliation: Wales Heart Research Institute, Cardiff University School of Medicine, Heath Park, Cardiff, Pontypridd, UK.
authors.forename: Philip E
authors.initials: PE
authors.lastname: James
authors.affiliation: Centre for Public Health, Nutrition and Metabolism Group, Queen's University Belfast, Belfast, UK.
authors.forename: Jane
authors.initials: J
authors.lastname: McEneny
authors.affiliation: Centre for Public Health, Nutrition and Metabolism Group, Queen's University Belfast, Belfast, UK.
authors.forename: Ian S
authors.initials: IS
authors.lastname: Young
authors.affiliation: Department of Biomedical Engineering, Toyo University, Kawagoe-Shi, Saitama, Japan.
authors.forename: Shigehiko
authors.initials: S
authors.lastname: Ogoh
authors.affiliation: Neurovascular Research Laboratory, Faculty of Life Sciences and Education, University of South Wales, Pontypridd, UK damian.bailey@southwales.ac.uk.
authors.forename: Damian M
authors.initials: DM
authors.lastname: Bailey
mesh_terms: D000293:Adolescent; D000328:Adult; D015444:Exercise / Q000502:physiology*; D017079:Exercise Tolerance / Q000502:physiology*; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D007249:Inflammation / Q000503:physiopathology*; D008297:Male; D055806:Microvessels / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology*; D010101:Oxygen Consumption / Q000502:physiology; D016037:Single-Blind Method; D055815:Young Adult