title: Reactive hyperemia is not responsible for stimulating muscle protein synthesis following blood flow restriction exercise.
abstract: Blood flow restriction (BFR) to contracting skeletal muscle during low-intensity resistance exercise training increases muscle strength and size in humans. However, the mechanism(s) underlying these effects are largely unknown. We have previously shown that mammalian target of rapamycin complex 1 (mTORC1) signaling and muscle protein synthesis (MPS) are stimulated following an acute bout of BFR exercise. The purpose of this study was to test the hypothesis that reactive hyperemia is the mechanism responsible for stimulating mTORC1 signaling and MPS following BFR exercise. Six young men (24 ± 2 yr) were used in a randomized crossover study consisting of two exercise trials: low-intensity resistance exercise with BFR (BFR trial) and low-intensity resistance exercise with sodium nitroprusside (SNP), a pharmacological vasodilator infusion into the femoral artery immediately after exercise to simulate the reactive hyperemia response after BFR exercise (SNP trial). Postexercise mixed-muscle fractional synthetic rate from the vastus lateralis increased by 49% in the BFR trial (P < 0.05) with no change in the SNP trial (P > 0.05). BFR exercise increased the phosphorylation of mTOR, S6 kinase 1, ribosomal protein S6, ERK1/2, and Mnk1-interacting kinase 1 (P < 0.05) with no changes in mTORC1 signaling in the SNP trial (P > 0.05). We conclude that reactive hyperemia is not a primary mechanism for BFR exercise-induced mTORC1 signaling and MPS. Further research is necessary to elucidate the cellular mechanism(s) responsible for the increase in mTOR signaling, MPS, and hypertrophy following acute and chronic BFR exercise.
authors.affiliation: The Univ. of Texas Medical Branch, Dept. of Nutrition and Metabolism, Division of Rehabilitation Sciences, 301 Univ. Blvd., Galveston, TX 77555-1124, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Gundermann
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Fry
authors.forename: Jared M
authors.initials: JM
authors.lastname: Dickinson
authors.forename: Dillon K
authors.initials: DK
authors.lastname: Walker
authors.forename: Kyle L
authors.initials: KL
authors.lastname: Timmerman
authors.forename: Micah J
authors.initials: MJ
authors.lastname: Drummond
authors.forename: Elena
authors.initials: E
authors.lastname: Volpi
authors.forename: Blake B
authors.initials: BB
authors.lastname: Rasmussen
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D018592:Cross-Over Studies; D005263:Femoral Artery; D005786:Gene Expression Regulation; D006339:Heart Rate; D006801:Humans; D006940:Hyperemia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D007261:Infusions, Intra-Arterial; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D019344:Lactic Acid / Q000097:blood; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D046912:Multiprotein Complexes; D009119:Muscle Contraction; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000235:genetics; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism* / Q000503:physiopathology; D009599:Nitroprusside / Q000008:administration & dosage; D010649:Phenylalanine / Q000097:blood; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D012039:Regional Blood Flow; D055070:Resistance Training; D038601:Ribosomal Protein S6 / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D013781:Texas; D013997:Time Factors; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D014665:Vasodilator Agents / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; D009124:Muscle Proteins; D011506:Proteins; D038601:Ribosomal Protein S6; D014665:Vasodilator Agents; D009599:Nitroprusside; D019344:Lactic Acid; D010649:Phenylalanine; D044767:Ubiquitin-Protein Ligases; C491395:MKNK1 protein, human; C546842:MTOR protein, human; D000076222:Mechanistic Target of Rapamycin Complex 1; D017346:Protein Serine-Threonine Kinases; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3