Sildenafil Enhances Muscle Synthesis

Overview

• Study Title: Sildenafil Increases Muscle Protein Synthesis and Reduces Muscle Fatigue.
• Type: Randomized controlled trial, published Clin Transl Sci. 2013 Dec;6(6):463-8.
• Main finding: Short-term daily sildenafil increased skeletal muscle protein synthesis, altered protein expression and S-nitrosylation, and reduced muscle fatigue.
• Mechanism proposed: Augmentation of nitric oxide–cGMP signaling via PDE5 inhibition.

Study Design and Methods

• Design: Randomized, placebo-controlled clinical trial with short-term daily sildenafil administration.
• Primary assessments: Muscle protein synthesis (fractional synthesis rate), protein expression and S‑nitrosylation, and muscle function tests.
• Functional tests: Isometric and isokinetic knee extensor strength via dynamometry; fatiguing isokinetic contractions (120°/s).
• Biopsy analysis: Skeletal muscle proteome and S‑nitrosylation profiling; pathway analysis using Ingenuity Pathways Analysis (IPA).

Participants

• Sample size reported in figures: Placebo N = 6, Sildenafil N = 5 for functional and synthesis comparisons.
• Participant characteristics beyond group numbers not specified in transcript.

Key Results

• Muscle Protein Synthesis:
  • Fractional synthesis rate increased after 8 days of sildenafil versus placebo (p = 0.004).
• Muscle Function:
  • Reduced fatigue: Increased successful repetitions during fatiguing isokinetic contractions after sildenafil (p = 0.016).
  • Isometric and isokinetic strength reported as percent of baseline; group differences shown in figures.
• Proteome and S‑Nitrosylation:
  • Sildenafil altered protein expression and S‑nitrosylation patterns in muscle biopsies.
  • Top canonical and functional pathways affected were identified via IPA (top six shown).

Interpretation

• Short-term PDE5 inhibition with sildenafil enhances muscle protein anabolism and reduces fatigue in human skeletal muscle.
• Effects attributed to increased NO–cGMP signaling impacting excitation–contraction coupling, myofibrillar function, perfusion, and metabolism.
• Authors suggest PDE5 inhibitors as potential pharmacologic interventions to improve impaired muscle function.

Decisions

• Conclusion by authors: PDE5 inhibitors represent viable pharmacologic interventions to improve skeletal muscle function.

Action Items

• Consider further larger-scale trials to confirm findings and assess long-term safety and functional outcomes.
• Explore mechanism-focused studies on NO–cGMP effects on excitation–contraction coupling and S‑nitrosylation in muscle.

Structured Details