Effects of combined treatment with blood flow restriction and low current electrical stimulation on capillary regression in the soleus muscle of diabetic rats
To clarify the preventive effects of low current electrical stimulation (ES) under blood flow restriction (Bfr) on diabetes-associated capillary regression in skeletal muscles, we assessed the changes in three-dimensional capillary architecture and angiogenic factors. Twenty-four Goto-Kakizaki rats were randomly divided into four groups: the sedentary diabetes mellitus (DM), Bfr (DM+Bfr), electrical stimulation (DM+ES), and Bfr plus ES (DM+Bfr+ES) groups. Six healthy Wistar rats were used as age-matched controls. Bfr was performed using pressure cuffs (80 mmHg) around the thighs of the rats, and low-current ES was applied to the calf muscles of the rats. The current intensity was set at 30% of the maximal isometric contraction (24-30 mA). The treatments were delivered three times a week for eight weeks. In the DM group, the capillary diameter and volume of the soleus muscle decreased, and, the anti-angiogenic factor level increased. Furthermore, DM caused an increase in the hypoxia-inducible factor. Individually, Bfr or ES treatments failed to inhibit the DM-associated capillary regression and increase in anti-angiogenic factor. However, combined treatment with Bfr and ES prevented DM-associated capillary regression via inhibition of the increased anti-angiogenic factor and enhancement of interleukin-15 expression, mitochondrial biogenesis factors, and a pro-angiogenic factor. Therefore, DM-associated capillary regression inhibited by the combined treatment may prevent the effects of the increased anti-angiogenic factor and enhance the pro-angiogenic factor.