title: Dietary nitrate reduces muscle metabolic perturbation and improves exercise tolerance in hypoxia.
abstract: Exercise in hypoxia is associated with reduced muscle oxidative function and impaired exercise tolerance. We hypothesised that dietary nitrate supplementation (which increases plasma [nitrite] and thus NO bioavailability) would ameliorate the adverse effects of hypoxia on muscle metabolism and oxidative function. In a double-blind, randomised crossover study, nine healthy subjects completed knee-extension exercise to the limit of tolerance (T(lim)), once in normoxia (20.9% O(2); CON) and twice in hypoxia (14.5% O(2)). During 24 h prior to the hypoxia trials, subjects consumed 0.75 L of nitrate-rich beetroot juice (9.3 mmol nitrate; H-BR) or 0.75 L of nitrate-depleted beetroot juice as a placebo (0.006 mmol nitrate; H-PL). Muscle metabolism was assessed using calibrated (31)P-MRS. Plasma [nitrite] was elevated (P < 0.01) following BR (194 ± 51 nm) compared to PL (129 ± 23 nm) and CON (142 ± 37 nM). T(lim) was reduced in H-PL compared to CON (393 ± 169 vs. 471 ± 200 s; P < 0.05) but was not different between CON and H-BR (477 ± 200 s). The muscle [PCr], [P(i)] and pH changed at a faster rate in H-PL compared to CON and H-BR. The [PCr] recovery time constant was greater (P < 0.01) in H-PL (29 ± 5 s) compared to CON (23 ± 5 s) and H-BR (24 ± 5 s). Nitrate supplementation reduced muscle metabolic perturbation during exercise in hypoxia and restored exercise tolerance and oxidative function to values observed in normoxia. The results suggest that augmenting the nitrate-nitrite-NO pathway may have important therapeutic applications for improving muscle energetics and functional capacity in hypoxia.
authors.affiliation: College of Life and Environmental Sciences, University of Exeter School of Sport and Health Sciences, Heavitree Road, St Luke's Campus, Exeter EX1 2LU, UK. a.vanhatalo@exeter.ac.uk
authors.forename: Anni
authors.initials: A
authors.lastname: Vanhatalo
authors.forename: Jonathan
authors.initials: J
authors.lastname: Fulford
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Bailey
authors.forename: James R
authors.initials: JR
authors.lastname: Blackwell
authors.forename: Paul G
authors.initials: PG
authors.lastname: Winyard
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Jones
mesh_terms: D000328:Adult; D027461:Beta vulgaris; D001794:Blood Pressure; D018592:Cross-Over Studies; D019587:Dietary Supplements; D004311:Double-Blind Method; D005080:Exercise Test; D017079:Exercise Tolerance / Q000187:drug effects*; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000503:physiopathology; D009566:Nitrates / Q000494:pharmacology*; D009573:Nitrites / Q000097:blood; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D018517:Plant Roots / Q000737:chemistry; D055815:Young Adult
chemical_list: D009566:Nitrates; D009573:Nitrites; D010936:Plant Extracts