Repeated maximal-intensity hypoxic exercise superimposed to hypoxic residence boosts skeletal muscle transcriptional responses in elite team-sport athletes.

AIM: To determine whether repeated maximal-intensity hypoxic exercise induces larger beneficial adaptations on the hypoxia-inducible factor-1α pathway and its target genes than similar normoxic exercise, when combined with chronic hypoxic exposure. METHODS: Lowland elite male team-sport athletes underwent 14 days of passive normobaric hypoxic exposure [≥14 h·day-1 at inspired oxygen fraction (Fi O2 ) 14.5-14.2%] with the addition of six maximal-intensity exercise sessions either in normobaric hypoxia (Fi O2 ~14.2%; LHTLH; n = 9) or in normoxia (Fi O2 20.9%; LHTL; n = 11). A group living in normoxia with no additional maximal-intensity exercise (LLTL; n = 10) served as control. Before (Pre), immediately after (Post-1) and 3 weeks after (Post-2) the intervention, muscle biopsies were obtained from the vastus lateralis. RESULTS: Hypoxia-inducible factor-1α subunit, vascular endothelial growth factor, myoglobin, peroxisome proliferator-activated receptor-gamma coactivator 1-α and mitochondrial transcription factor A mRNA levels increased at Post-1 (all P ≤ 0.05) in LHTLH, but not in LHTL or LLTL, and returned near baseline levels at Post-2. The protein expression of citrate synthase increased in LHTLH (P < 0.001 and P < 0.01 at Post-1 and Post-2, respectively) and LLTL (P < 0.01 and P < 0.05 at Post-1 and Post-2, respectively), whereas it decreased in LHTL at Post-1 and Post-2 (both P < 0.001). CONCLUSION: Combined with residence in normobaric hypoxia, repeated maximal-intensity hypoxic exercise induces short-term post-intervention beneficial changes in muscle transcriptional factors that are of larger magnitude (or not observed) than with similar normoxic exercise. The decay of molecular adaptations was relatively fast, with most of benefits already absent 3 weeks post-intervention.

No effect of dietary nitrate supplementation on endurance training in hypoxia.

We investigated whether dietary nitrate (NO(3)(-)) supplementation enhances the effect of training in hypoxia on endurance performance at sea level. Twenty-two healthy male volunteers performed high-intensity endurance training on a cycle ergometer (6 weeks, 5×30 min/week at 4-6 mmol/L blood lactate) in normobaric hypoxia (12.5% FiO(2)), while ingesting either beetroot juice [0.07 mmol NO(3)(-) /kg body weight (bw)/day; BR, n = 11] or a control drink (CON, n = 11). During the pretest and the posttest, the subjects performed a 30-min simulated time trial (TT) and an incremental VO(2max) test. Furthermore, a biopsy was taken from m. vastus lateralis before and after the TT. Power output during the training sessions in both groups increased by ∼6% from week 1 to week 6 (P < 0.05). Compared with the pretest, VO(2max) in the posttest was increased (P < 0.05) in CON (5%) and BR (9%). Power output corresponding with the 4 mmol/L blood lactate threshold, as well as mean power output during TT increased by ∼16% in both groups (P < 0.05). Muscle phospho-AMP-activated protein kinase, hypoxia inducible factor-1α mRNA content, and glycogen breakdown during the TT were similar between the groups in both the pretest and the posttest. In conclusion, low-dose dietary NO(3)(-) supplementation does not enhance the effects of intermittent hypoxic training on endurance exercise performance at sea level.

Effect of acute environmental hypoxia on protein metabolism in human skeletal muscle.

UNLABELLED: Hypoxia-induced muscle wasting has been observed in several environmental and pathological conditions. However, the molecular mechanisms behind this loss of muscle mass are far from being completely elucidated, certainly in vivo. When studying the regulation of muscle mass by environmental hypoxia, many confounding factors have to be taken into account, such as decreased protein ingestion, sleep deprivation or reduced physical activity, which make difficult to know whether hypoxia per se causes a reduction in muscle mass. AIM: We hypothesized that acute exposure to normobaric hypoxia (11% O2 ) would repress the activation of the mTOR pathway usually observed after a meal and would activate the proteolytic pathways in skeletal muscle. METHODS: Fifteen subjects were exposed passively for 4 h to normoxic and hypoxic conditions in a random order after consumption of a light breakfast. A muscle biopsy and a blood sample were taken before, after 1 and 4 h of exposure. RESULTS: After 4 h, plasma insulin concentration and the phosphorylation state of PKB and S6K1 in skeletal muscle were higher in hypoxia than in normoxia (P < 0.05). At the same time, Redd1 mRNA level was upregulated (P < 0.05), whilst MAFbx mRNA decreased (P < 0.05) in hypoxia compared with normoxia. Proteasome, cathepsin L and calpain activities were not altered by environmental hypoxia. CONCLUSION: Contrary to our hypothesis and despite an increase in the mRNA level of Redd1, an inhibitor of the mTORC1 pathway, short-term acute environmental hypoxia induced a higher response of PKB and S6K1 to a meal, which may be due to increased plasma insulin concentration.