Conditions: Fatigue
Keywords: Fatigue Fatigability Surface Electromyography (sEMG) cyclic guanosine monophosphate (cGMP) Nitric Oxide (NO) NO-cGMP Phosphodiesterase (PDE) Sildenafil Tadalafil Isotope Infusion Anabolism Upregulation Accelerometer Placebo Nitrosylation
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 30
Healthy volunteers: yes

Brief summary:
This study is funded by the Moody Endowment. In this project, we will investigate the potential effect of skeletal muscle nitric oxide (NO) production on skeletal muscle anabolism, muscle strength, physical function, and body composition in older individuals. Further, we will determine whether augmentation of NO-mediated signaling reduces fatigue and fatigability.

Detailed description:
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

Arms:
arm 1: 50 mg/day Sildenafil: (Other Name: Viagra, Revatio) for weeks 0-4. Placebo for weeks 5-8. arm 2: 10 mg/day Tadalafil: (Other Name: Cialis, Adcirca) for weeks 0-4. Placebo for weeks 5-8. arm 3: Placebo for weeks 0-4. 50 mg/day Sildenafil: (Other Name: Viagra, Revatio) for weeks 5-8. arm 4: Placebo for weeks 0-4. 10 mg/day Tadalafil: (Other Name: Cialis, Adcirca) for weeks 5-8.

Interventions: intervention 1: Sildenafil intervention 2: tadalafil intervention 3: Placebo
Intervention descriptions: intervention 1: 50 mg/day for 4 weeks intervention 2: 10 mg/day for 4 weeks. intervention 3: Placebo 1 capsule per day for four weeks.

Protocol document: