Effects of systemic hypoxia on human muscular adaptations to resistance exercise training

Abstract

Hypoxia is an important modulator of endurance exercise-induced oxidative adaptations in skeletal muscle. However, whether hypoxia affects resistance exercise-induced muscle adaptations remains unknown. Here, we determined the effect of resistance exercise training under systemic hypoxia on muscular adaptations known to occur following both resistance and endurance exercise training, including muscle cross-sectional area (CSA), one-repetition maximum (1RM), muscular endurance, and makers of mitochondrial biogenesis and angiogenesis, such as peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), citrate synthase (CS) activity, nitric oxide synthase (NOS), vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1 (HIF-1), and capillary-to-fiber ratio. Sixteen healthy male subjects were randomly assigned to either a normoxic resistance training group (NRT, n = 7) or a hypoxic (14.4% oxygen) resistance training group (HRT, n = 9) and performed 8 weeks of resistance training. Blood and muscle biopsy samples were obtained before and after training. After training muscle CSA of the femoral region, 1RM for bench-press and leg-press, muscular endurance, and skeletal muscle VEGF protein levels significantly increased in both groups. The increase in muscular endurance was significantly higher in the HRT group. Plasma VEGF concentration and skeletal muscle capillary-to-fiber ratio were significantly higher in the HRT group than the NRT group following training. Our results suggest that, in addition to increases in muscle size and strength, HRT may also lead to increased muscular endurance and the promotion of angiogenesis in skeletal muscle.

Keywords: Capillarization; resistance exercise training; skeletal muscle; systemic hypoxia.

Figure 1.

Changes in muscle cross‐sectional area (CSA) and one‐repetition maximum (1RM) of bench‐press and leg‐press before (baseline) and after (8 weeks) the resistance training program. NRT, normoxic resistance training (n =7); HRT, hypoxic resistance training (n =9). Significantly different from baseline: **P <0.01.

Figure 2.

Changes in exercise volume during leg‐press exercises at 70% of 1RM before (baseline) and after (8 weeks) the resistance training program. NRT, normoxic resistance training (n =7); HRT, hypoxic resistance training (n =9). Values are represented as means ± SE. Significantly different from baseline: **P <0.01; significantly different from NRT: ^#P <0.05.

Figure 3.

Changes in pulse oximetry oxygen saturation (SpO₂) and growth hormone concentrations before and after the resistance exercises. NRT, normoxic resistance training (n =7); HRT, hypoxic resistance training (n =9). Values are represented as means ± SE. Significantly different from pre 1: ^†P <0.05; ^††P <0.01; significantly different from pre 2: *P <0.05; **P <0.01; significantly different from NRT: ^##P <0.01. Resistance exercise is denoted as a shaded area.

Figure 4.

Changes in plasma vascular endothelial growth factor (VEGF) before (baseline), during (4 weeks), and after (8 weeks) the resistance training program. NRT, normoxic resistance training (n =7); HRT, hypoxic resistance training (n =9). Values are represented as means ± SE. Significantly different from baseline: **P <0.01; significantly different from NRT: ^##P <0.01.

Figure 5.

Hypoxia‐inducible factor 1 alpha (HIF‐1α), vascular endothelial growth factor (VEGF), VEGF receptor 1 (FLT‐1), and peroxisome proliferator‐activated receptor‐γ coactivator‐1α (PGC‐1α) mRNA expressions in skeletal muscle before (baseline) and after (8 weeks) the resistance training program. NRT, normoxic resistance training (n =7); HRT, hypoxic resistance training (n =9). Values are represented as means ± SE.

Figure 6.

Endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), vascular endothelial growth factor‐B (VEGF‐B), and peroxisome proliferator‐activated receptor‐γ coactivator‐1α (PGC‐1α) protein expressions in skeletal muscle before (baseline) and after (8 weeks) the resistance training program. NRT, normoxic resistance training (n =7); HRT, hypoxic resistance training (n =9). Values are represented as means ± SE.

Figure 7.

Change in citrate synthase (CS) activity before (baseline) and after (8 weeks) the resistance training program. NRT, normoxic resistance training (n =7); HRT, hypoxic resistance training (n =9). Values are represented as means ± SE. Significantly different from baseline: *P <0.05.

Figure 8.

(A) Immunofluorescence staining of endothelial cells with anti‐CD31 antibody and fluorescein‐conjugated secondary antibody (green) in skeletal muscle before (baseline) and after (8 weeks) the resistance training program. (B) Capillary‐to‐fiber ratio before (baseline) and after (8 weeks) training program. NRT, normoxic resistance training (n =6); HRT, hypoxic resistance training (n =6). Values are represented as means ± SE. Significantly different from baseline: **P <0.01; significantly different from NRT: ^#P <0.05.