• Open Access

Sildenafil Increases Muscle Protein Synthesis and Reduces Muscle Fatigue

Authors

  • Melinda Sheffield-Moore Ph.D.,

    1. Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, USA
    Search for more papers by this author
  • John E. Wiktorowicz Ph.D.,

    1. Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA
    2. Sealy Center for Molecular Medicine, University of Texas Medical Branch, Galveston, Texas, USA
    Search for more papers by this author
  • Kizhake V. Soman Ph.D.,

    1. Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA
    2. Sealy Center for Molecular Medicine, University of Texas Medical Branch, Galveston, Texas, USA
    Search for more papers by this author
  • Christopher P. Danesi M.S.,

    1. Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, USA
    2. Department of Rehabilitation Sciences, University of Texas Medical Branch, Galveston, Texas, USA
    Search for more papers by this author
  • Michael P. Kinsky M.D.,

    1. Department of Anesthesiology, University of Texas Medical Branch, Galveston, Texas, USA
    Search for more papers by this author
  • Edgar L. Dillon Ph.D.,

    1. Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, USA
    Search for more papers by this author
  • Kathleen M. Randolph B.S.,

    1. Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, USA
    Search for more papers by this author
  • Shannon L. Casperson Ph.D.,

    1. Department of Cell Biology, University of Texas Medical Branch, Galveston, Texas, USA
    Current affiliation:
    1. Grand Forks Human Nutrition Research Center, Grand Forks, North Dakota, USA
    Search for more papers by this author
  • Dennis C. Gore M.D.,

    1. Department of Surgery, University of Texas Medical Branch, Galveston, Texas, USA
    Search for more papers by this author
  • Astrid M. Horstman Ph.D.,

    1. Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, USA
    Current affiliation:
    1. German Aerospace Center, Institute of Aerospace Medicine, Department Space Physiology, Cologne, Germany
    Search for more papers by this author
  • James P. Lynch B.S.,

    1. Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, USA
    Search for more papers by this author
  • Barbara M. Doucet Ph.D.,

    1. Department of Rehabilitation Sciences, University of Texas Medical Branch, Galveston, Texas, USA
    Search for more papers by this author
  • Joni A. Mettler Ph.D.,

    1. Department of Rehabilitation Sciences, University of Texas Medical Branch, Galveston, Texas, USA
    Current affiliation:
    1. Department of Health and Human Performance, Texas State University, San Marcos, Texas, USA
    Search for more papers by this author
  • Jeffrey W. Ryder Ph.D.,

    1. Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, USA
    2. Universities Space Research Association, Houston, Texas, USA
    Search for more papers by this author
  • Lori L. Ploutz-Snyder Ph.D.,

    1. Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, USA
    2. Universities Space Research Association, Houston, Texas, USA
    Search for more papers by this author
  • Jean W. Hsu Ph.D.,

    1. USDA/ARS, Children's Nutrition Research Center, Dept of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
    Search for more papers by this author
  • Farook Jahoor Ph.D.,

    1. USDA/ARS, Children's Nutrition Research Center, Dept of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
    Search for more papers by this author
  • Kristofer Jennings Ph.D.,

    1. Department of Preventive Medicine and Community Health (Epidemiology & Biostatistics), University of Texas Medical Branch, Galveston, Texas, USA
    Search for more papers by this author
  • Gregory R. White M.D.,

    1. Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, USA
    Search for more papers by this author
  • Susan D. McCammon M.D.,

    1. Department of Otolaryngology, University of Texas Medical Branch, Galveston, Texas, USA
    Search for more papers by this author
  • William J. Durham Ph.D.

    Corresponding author
    1. Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, USA
    Search for more papers by this author

Abstract

Reductions in skeletal muscle function occur during the course of healthy aging as well as with bed rest or diverse diseases such as cancer, muscular dystrophy, and heart failure. However, there are no accepted pharmacologic therapies to improve impaired skeletal muscle function. Nitric oxide may influence skeletal muscle function through effects on excitation-contraction coupling, myofibrillar function, perfusion, and metabolism. Here we show that augmentation of nitric oxide-cyclic guanosine monophosphate signaling by short-term daily administration of the phosphodiesterase 5 inhibitor sildenafil increases protein synthesis, alters protein expression and nitrosylation, and reduces fatigue in human skeletal muscle. These findings suggest that phosphodiesterase 5 inhibitors represent viable pharmacologic interventions to improve muscle function.

Ancillary