title: Sildenafil increases muscle protein synthesis and reduces muscle fatigue.
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.
authors: Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, USA.
authors: Melinda
authors: M
authors: Sheffield-Moore
authors: John E
authors: JE
authors: Wiktorowicz
authors: Kizhake V
authors: KV
authors: Soman
authors: Christopher P
authors: CP
authors: Danesi
authors: Michael P
authors: MP
authors: Kinsky
authors: Edgar L
authors: EL
authors: Dillon
authors: Kathleen M
authors: KM
authors: Randolph
authors: Shannon L
authors: SL
authors: Casperson
authors: Dennis C
authors: DC
authors: Gore
authors: Astrid M
authors: AM
authors: Horstman
authors: James P
authors: JP
authors: Lynch
authors: Barbara M
authors: BM
authors: Doucet
authors: Joni A
authors: JA
authors: Mettler
authors: Jeffrey W
authors: JW
authors: Ryder
authors: Lori L
authors: LL
authors: Ploutz-Snyder
authors: Jean W
authors: JW
authors: Hsu
authors: Farook
authors: F
authors: Jahoor
authors: Kristofer
authors: K
authors: Jennings
authors: Gregory R
authors: GR
authors: White
authors: Susan D
authors: SD
authors: McCammon
authors: William J
authors: WJ
authors: Durham
mesh_terms: D000328:Adult; D000368:Aged; D006152:Cyclic GMP / Q000378:metabolism; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D006801:Humans; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects*; D018763:Muscle Fatigue / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology; D009569:Nitric Oxide / Q000378:metabolism; D058986:Phosphodiesterase 5 Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use*; D014176:Protein Biosynthesis / Q000187:drug effects*; D011687:Purines / Q000008:administration & dosage / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage / Q000627:therapeutic use*; D013781:Texas; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D009569:Nitric Oxide; D000068677:Sildenafil Citrate; D006152:Cyclic GMP
keywords: exercise; metabolism; protein S-nitrosylation; translational research