The Effect of Sildenafil and Tadalafil on Skeletal Muscle and Perceptual Fatigue

The Investigators hypothesize that upregulation of skeletal muscle NO-cGMP mediated responses through phosphodiesterase (PDE) inhibition by sildenafil or tadalafil causes an acute anabolic response of skeletal muscle protein synthesis. NO is well-known to elicit vasodilation through stimulation of cGMP signaling, and NO-mediated changes in muscle perfusion may influence both skeletal muscle anabolism and perceptual fatigue. To measure skeletal muscle protein synthesis, we will infuse a stable isotope tracer of phenylalanine and measure its incorporation into skeletal muscle proteins following a dose of sildenafil, tadalafil, or placebo. The Investigators will also determine whether differences exist between men and women in response to PDE inhibition. As skeletal muscle NO-cGMP signaling has been implicated in fatigue responses, we will assess the acute effect of sildenafil and tadalafil on fatigue. Fatigue can be manifested both as a performance deficit at a local level (e.g., a reduced ability of skeletal muscle to produce power or force) as well as a subjective experience of lacking physical or mental energy. Accordingly, we will use more than one means (skeletal muscle performance, fatigue questionnaires, accelerometers) to study fatigue. The Investigators hypothesize that sildenafil or tadalafil will acutely reduce exercise-associated fatigability and skeletal muscle fatigue development