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Sildenafil Increases Muscle Protein Synthesis and Reduces Muscle Fatigue
Melinda Sheffield‐Moore, Ph.D., John E. Wiktorowicz, Ph.D., [...], and William J. Durham, Ph.D.
In this study we found that short‐term treatment with the phosphodiesterase 5 inhibitor sildenafil reduces skeletal muscle fatigue and stimulates skeletal muscle protein synthesis while altering muscle protein expression and nitrosylation. Our findings thus provide evidence that sildenafil remodels human skeletal muscle in a functionally adaptive manner.
As a determinant of the amount and composition of skeletal muscle proteins, protein synthesis can affect skeletal muscle function through changes in both the mass and quality of muscle. The differences between treatment groups in protein abundance and S‐nitrosylation observed in this study suggest that changes in myofibrillar function and actin dynamics may have contributed to an increase in muscle quality, manifested as increased fatigue resistance, in individuals receiving sildenafil. Notably, the approximate doubling of skeletal muscle protein synthesis observed in response to sildenafil is of similar magnitude to that observed in response to 100–200 mg/week testosterone injection,
31,
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33 an intervention which increases skeletal muscle mass and strength
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34 but does not reduce muscle fatigability,
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35 with long‐term administration. Whether the short‐term responses of protein synthesis and expression eventually manifest as a change in muscle mass or simply reflect an adaptive qualitative change in muscle protein composition will be important to determine in future longer‐term studies.