title: Supplementing essential amino acids with the nitric oxide precursor, l-arginine, enhances skeletal muscle perfusion without impacting anabolism in older men.
abstract: Postprandial limb blood flow and skeletal muscle microvascular perfusion reduce with aging. Here we tested the impact of providing bolus essential amino acids (EAA) in the presence and absence of the nitric oxide precursor, l-Arginine (ARG), upon skeletal muscle blood flow and anabolism in older men. Healthy young (YOUNG: 19.7 ± 0.5 y, N = 8) and older men (OLD, 70 ± 0.8 y, N = 8) received 15 g EAA or (older only) 15 g EAA +3 g ARG (OLD-ARG, 69.2 ± 1.2 y, N = 8). We quantified responses in muscle protein synthesis (MPS; incorporation of13C phenylalanine into myofibrillar proteins), leg and muscle microvascular blood flow (Doppler/contrast enhanced ultrasound (CEUS)) and insulin/EAA in response to EEA ± ARG. Plasma EAA increased similarly across groups but argininemia was evident solely in OLD-ARG (∼320 mmol, 65 min post feed); increases in plasma insulin (to ∼13 IU ml-1) were similar across groups. Increases in femoral flow were evident in YOUNG >2 h after feeding; these effects were blunted in OLD and OLD-ARG. Increases in microvascular blood volume (MBV) occurred only in YOUNG and these effects were isolated to the early postprandial phase (+45% at ∼45 min after feeding) coinciding with detectable arterio-venous differences in EAA reflecting net uptake by muscle. Increases in microvascular flow velocity (MFV) and tissue perfusion (MBV × MFV) occurred (∼2 h) in YOUNG and OLD-ARG, but not OLD. Postprandial protein accretion was greater in YOUNG than OLD or OLD-ARG; the latter two groups being indistinguishable. Therefore, ARG rescues aspects of muscle perfusion in OLD without impacting anabolic blunting, perhaps due to the "rescue" being beyond the period of active EAA-uptake.
authors.affiliation: MRC-ARUK Centre of Excellence for Musculoskeletal Ageing Research, School of Medicine, University of Nottingham, Derby, DE22 3DT, UK.
authors.forename: W Kyle
authors.initials: WK
authors.lastname: Mitchell
authors.affiliation: MRC-ARUK Centre of Excellence for Musculoskeletal Ageing Research, School of Medicine, University of Nottingham, Derby, DE22 3DT, UK.
authors.forename: Bethan E
authors.initials: BE
authors.lastname: Phillips
authors.affiliation: MRC-ARUK Centre of Excellence for Musculoskeletal Ageing Research, School of Medicine, University of Nottingham, Derby, DE22 3DT, UK.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Wilkinson
authors.affiliation: MRC-ARUK Centre of Excellence for Musculoskeletal Ageing Research, School of Medicine, University of Nottingham, Derby, DE22 3DT, UK.
authors.forename: John P
authors.initials: JP
authors.lastname: Williams
authors.affiliation: MRC-ARUK Centre of Excellence for Musculoskeletal Ageing Research, School of Medicine, University of Nottingham, Derby, DE22 3DT, UK.
authors.forename: Debbie
authors.initials: D
authors.lastname: Rankin
authors.affiliation: MRC-ARUK Centre of Excellence for Musculoskeletal Ageing Research, School of Medicine, University of Nottingham, Derby, DE22 3DT, UK.
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Lund
authors.affiliation: MRC-ARUK Centre of Excellence for Musculoskeletal Ageing Research, School of Medicine, University of Nottingham, Derby, DE22 3DT, UK.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Smith
authors.affiliation: MRC-ARUK Centre of Excellence for Musculoskeletal Ageing Research, School of Medicine, University of Nottingham, Derby, DE22 3DT, UK. Electronic address: Philip.atherton@nottingham.ac.uk.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Atherton
mesh_terms: D000367:Age Factors; D000368:Aged; D000601:Amino Acids, Essential / Q000008:administration & dosage* / Q000097:blood; D001120:Arginine / Q000008:administration & dosage* / Q000097:blood; D015992:Body Mass Index; D019587:Dietary Supplements; D018737:Hand Strength; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects; D009210:Myofibrils / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010649:Phenylalanine / Q000008:administration & dosage / Q000097:blood; D019518:Postprandial Period; D014176:Protein Biosynthesis; D012039:Regional Blood Flow; D055815:Young Adult
chemical_list: D000601:Amino Acids, Essential; D007328:Insulin; D009124:Muscle Proteins; D009569:Nitric Oxide; D010649:Phenylalanine; D001120:Arginine
keywords: Ageing; Arginine; Blood flow; Metabolism; Muscle; Nutrition