Effects of Exercise Preconditioning on the Microvasculature of Atrophied Muscle

Abstract

Much less is known about the coupling between microvasculature and muscle disuse atrophy, although atrophy is characterized by a decrease in muscle volume, mass, and strength. Muscle atrophy induced structural alterations in the microvascular network, an apoptosis of endothelial cell of the muscle, and hemodynamic disturbance in microvasculature. PURPOSE: We have investigated the mechanism of exercise to prevent structural alterations of the microvascular network through the gene expression of angiogenesisrelated factors in the rat soleus muscle following hindlimb unloading (HU) with exercise preconditioning(ExP). METHODS: Wistar rats were randomly divided into an age-matched control group, a hindlimb unloading for 2-wk without and with ExP. The rats in the ExP groups were trained to run on a motor-driven treadmill before HU. To clarify threedimensional architecture of microvascular network, contrast medium-injected sections were visualized clearly with a confocal laser scanning microscope. The mRNAs for angiogenesis-related factors, including HIF-1 alfa, VEGF, KDR/Flk-1, Flt-1, angiopoietin-1, 2, Tie-2, TSP-1, were analyzed using a real time quantitative PCR. RESULTS: After HU, the mean capillary density, the number of anastomotic capillaries, the tortuosity of capillaries and capillary luminal diameter were significantly smaller than in control. However, in HU with exercise preconditioning, these were significantly higher compared with HU. Real time PCR analysis showed that the expression of angiogenic factor mRNAs were decreased in HU than in control muscles. The expression levels of the angiogenic genes were higher in the ExP than the unloading muscles. Especially, the expression levels of KDR/Flk-1, and Tie-2 genes were higher in the ExP. CONCLUSIONS: Although HU conditions induced significant reduction of the microvascular network with decreased angiogenic factors, results from the present investigation indicate that the exercise preconditioning attenuated the regression of muscle microvasculature in hindlimb unloading rats. These findings indicate that the application of exercise preconditioning might be an effective countermeasure to microvascular regression induced by hindlimb unloading. Supported by Grants-in-Aid for Science Research from the Japanese Ministry.