title: Passive leg movement and nitric oxide-mediated vascular function: the impact of age.
abstract: In young healthy men, passive leg movement (PLM) elicits a robust nitric oxide (NO)-dependent increase in leg blood flow (LBF), thus providing a novel approach to assess NO-mediated vascular function. While the magnitude of the LBF response to PLM is markedly reduced with age, the role of NO in this attenuated response in the elderly is unknown. Therefore, this study sought to determine the contribution of NO in the PLM-induced LBF with age. Fourteen male subjects (7 young, 24 ± 1 yr; and 7 old, 75 ± 3 yr) underwent PLM with and without NO synthase (NOS) inhibition achieved by intra-arterial infusion of N(G)-monomethyl-L-arginine (L-NMMA). LBF was determined second-by-second by Doppler ultrasound, and central hemodynamics were measured by finger photoplethysmography. NOS inhibition blunted the PLM-induced peak increase in LBF in the young (control: 668 ± 106;
  431 ± 95 Δml/min; P = 0.03) but had no effect in the old (control: 266 ± 98;
  251 ± 92 Δml/min; P = 0.59). Likewise, the magnitude of the reduction in the overall (i.e., area under the curve) PLM-induced LBF response to NOS inhibition was less in the old (LBF: -31 ± 18 ml) than the young (LBF: -129 ± 21 ml; P < 0.01). These findings suggest that the age-associated reduction in PLM-induced LBF in the elderly is primarily due to a reduced contribution to vasodilation from NO and therefore support the use of PLM as a novel approach to assess NO-mediated vascular function across the lifespan.
authors.affiliation: Geriatric Research Education and Clinical Center, George E. Wahlen, Veteran Affairs Medical Center, Salt Lake City, Utah; Department of Internal Medicine, Division of Geriatrics, University of Utah, Salt Lake City, Utah; joel.trinity@utah.edu.
authors.forename: Joel D
authors.initials: JD
authors.lastname: Trinity
authors.affiliation: Department of Exercise and Sport Science, University of Utah, Salt Lake City, Utah;
authors.forename: H Jonathan
authors.initials: HJ
authors.lastname: Groot
authors.affiliation: Department of Internal Medicine, Division of Geriatrics, University of Utah, Salt Lake City, Utah;
authors.forename: Gwenael
authors.initials: G
authors.lastname: Layec
authors.affiliation: Department of Exercise and Sport Science, University of Utah, Salt Lake City, Utah;
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Rossman
authors.affiliation: Geriatric Research Education and Clinical Center, George E. Wahlen, Veteran Affairs Medical Center, Salt Lake City, Utah; Department of Internal Medicine, Division of Geriatrics, University of Utah, Salt Lake City, Utah; Department of Health and Exercise Sciences, Skidmore College, Saratoga Springs, New York.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Ives
authors.affiliation: Department of Anesthesia, University of Utah, Salt Lake City, Utah; and.
authors.forename: David E
authors.initials: DE
authors.lastname: Morgan
authors.affiliation: Department of Anesthesia, University of Utah, Salt Lake City, Utah; and.
authors.forename: Ben S
authors.initials: BS
authors.lastname: Gmelch
authors.affiliation: Department of Anesthesia, University of Utah, Salt Lake City, Utah; and.
authors.forename: Amber
authors.initials: A
authors.lastname: Bledsoe
authors.affiliation: Geriatric Research Education and Clinical Center, George E. Wahlen, Veteran Affairs Medical Center, Salt Lake City, Utah; Department of Internal Medicine, Division of Geriatrics, University of Utah, Salt Lake City, Utah; Department of Exercise and Sport Science, University of Utah, Salt Lake City, Utah;
authors.forename: Russell S
authors.initials: RS
authors.lastname: Richardson
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D062186:Arterial Pressure; D001783:Blood Flow Velocity; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005263:Femoral Artery / Q000000981:diagnostic imaging / Q000378:metabolism*; D006339:Heart Rate; D006801:Humans; D007261:Infusions, Intra-Arterial; D035002:Lower Extremity; D008297:Male; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D012039:Regional Blood Flow; D013318:Stroke Volume; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects; D055815:Young Adult; D019323:omega-N-Methylarginine / Q000008:administration & dosage
chemical_list: D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase
keywords: aging; endothelial function; flow-mediated dilation; leg blood flow; nitric oxide