This project will investigate whether exposing mice to tobacco smoke for 2 months, which leads to muscle capillary density regression and impairs fatigue resistance in mice, will interfere with muscle adaptations to exercise training. Cigarette smoking inhibits the production of several growth factors in muscles, including VEGF, a growth factor that stimulates capillary formation between muscle fibers. The regression of capillary bed in muscle is one of the main reasons muscle fatigues faster in mice exposed to cigarette smoke. Also, there is an effect of smoking on muscle function. It has been shown that exercise training has a very potent effect in increasing capillary bed in muscle (Delavar, et.al, 2014). Although there are other studies that show exercise training interferes with the inflammatory effects of smoking on muscle, it is not known whether exercise training can mitigate the effects of smoking on in vivo fatigue, capillaries, and muscle adaptation to training. The hypothesis is that exercise training decreases the pro-inflammatory signaling of smoking in muscle, blocking decreases in VEGF expression in muscle. Wild-type mice (n=8 per group) will be subjected to in vivo muscle contractions in one leg by electrically stimulating the distal peroneal nerve. The contralateral leg will be used as a non-stimulated control. The effects of repetitive contractions protocol in vivo on muscle cross-sectional area, capillarity, and ex-vivo intact muscle force will be evaluated. In addition, effects of 2-month smoke exposure will be investigated in another group mice after protocol of electrical stimulation. Results from this project will help understand whether beneficial effects of exercise training are affected by chronic smoking.