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.

Figures

Figure 1

Intramuscular [PCr] relative to resting baseline illustrated as group mean (error bars excluded for clarity), during low-intensity exercise in normoxia (CON), hypoxia following placebo supplementation (H-PL) and hypoxia following nitrate supplementation (H-BR)

Figure 2. Group mean intramuscular [PCr] (A) and [Pi] (B) during high-intensity exercise

The Tlim was significantly reduced in H-PL compared to (*P < 0.05). Error bars indicate SEM at task failure.

Figure 3. Group mean intramuscular [ADP] and pH during high-intensity exercise

Error bars indicate SEM at task failure. *Tlim less in the H-PL trial compared to H-BR and CON (P < 0.05).