Effects of endurance training with hypoxic stimulation induced by Co^<2+> treatment on oxygen transport system in rat skeletal muscles

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This study was designed to examine the changes in the capillary geometry and expression of angiogenic growth factor in skeletal muscles after endurance training with and without chronic CoCl_2 administration. The Co^<2+>-treated rats drank water containing 0.01% CoCl_2. In the first experiment, training and Co^<2+> administration lasted for 5 weeks. Chronic Co^<2+> administration significantly increased the blood hemoglobin concentration by approximately 25% with and without training. Only in the diaphragm, the Co^<2+> treatment alone significantly increased total capillary density and the capillary-to-fiber ratio (C:F). Both training groups with and without Co^<2+> administration significantly increased the C:F in soleus (SOL) and plantaris (PL) muscles. In PL, the increase was significantly greater in the Co^<2+>-treated training group than in the non-Co^<2+>-treated training group. The densities of VEGF-positive capillaries (VEGF-cap) remained unchanged in all muscle portions examin … More ed after either Co^<2+> administration or exercise training. The second experiment was designed to examine the time course changes in VEGF expression and capillary geometry in the early stage of the treatment. After 6 and 10 days of the Co^<2+> administration, the VEGF-cap was significantly increased by 27% and 65%, respectively in SOL. After 10 days of Co^<2+> administration, the C:F was significantly increased. The training with Co^<2+> significantly increased the VEGF-cap by 69%, 44% and 60%, respectively, after 3, 6 and 10 days in SOL, while it significantly increased the VEGF-cap after 10 days in the mixed fiber portion of plantaris muscle (PLm). Training with or without Co^<2+> significantly increased the C:F after 6 and 10 days in the SOL. Training with Co^<2+>, but training alone did not, significantly increased the C:F in PLm after 10 days. In condition, the present results suggest that activation of the cellular oxygen-sensing mechanism induced by Co^<2+> administration facilitates microvascular remodeling in hind-leg muscles by facilitating an expression of VEGF. Less