High-intensity interval training in hypoxia does not affect muscle HIF responses to acute hypoxia in humans

The myocellular response to hypoxia is primarily regulated by hypoxia-inducible factors (HIFs). HIFs thus conceivably are implicated in muscular adaptation to altitude training. Therefore, we investigated the effect of hypoxic versus normoxic training during a period of prolonged hypoxia ('living high') on muscle HIF activation during acute ischaemia. Ten young male volunteers lived in normobaric hypoxia for 5 weeks (5 days per week, similar to 15.5 h per day, FiO2: 16.4-14.0%). One leg was trained in hypoxia (TRHYP, 12.3% FiO2) whilst the other leg was trained in normoxia (TRNOR, 20.9% FiO2). Training sessions (3 per week) consisted of intermittent unilateral knee extensions at 20-25% of the 1-repetition maximum. Before and after the intervention, a 10-min arterial occlusion and reperfusion of the leg was performed. Muscle oxygenation status was continuously measured by near-infrared spectroscopy. Biopsies were taken from m. vastus lateralis before and at the end of the occlusion. Irrespective of training, occlusion elevated the fraction of HIF-1 alpha expressing myonuclei from similar to 54 to similar to 64% (P < 0.05). However, neither muscle HIF-1 alpha or HIF-2 alpha protein abundance, nor the expression of HIF-1 alpha or downstream targets selected increased in any experimental condition. Training in both TRNOR and TRHYP raised muscular oxygen extraction rate upon occlusion by similar to 30%, whilst muscle hyperperfusion immediately following the occlusion increased by similar to 25% in either group (P < 0.05). Ten minutes of arterial occlusion increased HIF-1 alpha-expressing myonuclei. However, neither normoxic nor hypoxic training during 'living high' altered muscle HIF translocation, stabilisation, or transcription in response to acute hypoxia induced by arterial occlusion.