Time‐course changes in VEGF expression and capillarity in the early stage of exercise training with Co2+ treatment in rat skeletal muscles

Aim: Cobalt administration was reported to mimic hypoxia. This study was designed to examine the time‐course changes in vascular endothelial growth factor (VEGF) expression and capillary geometry in skeletal muscles during endurance training with CoCl₂ administration in female Wistar rats. Methods: Exercise training by running lasted for up to 10 days at 25 m min^?1 on a 20% gradient, 15–42 min day^?1. Rats in the Co²⁺‐treated groups drank water containing 0.01% CoCl₂. Serial frozen sections were stained for alkaline phosphatase and dipeptidylpeptidase IV to identify capillary profiles and VEGF‐A protein. Results: In the soleus muscle, the density of VEGF‐positive capillaries (VEGF‐cap) was significantly increased after 6 and 10 days of the Co²⁺ administration (by 27 and 65% respectively) while the capillary‐to‐fibre ratio (C : F) first increased after 10 days. The training with Co²⁺ significantly increased VEGF‐cap by 69, 44 and 60%, respectively, after 3, 6 and 10 days. The VEGF‐cap was significantly increased after 6 and 10 days of training alone by 38 and 58%, respectively. In a similar extent, both training groups with and without Co²⁺ showed a significant increase in the C : F ratio after 6 and 10 days. Conclusions: The present results suggest that activation of the cellular oxygen‐sensing mechanism induced by Co²⁺ administration slightly facilitates an expression of VEGF but does not facilitate exercise‐induced microvascular remodelling in hind‐leg muscles.