title: Ascorbic acid improves brachial artery vasodilation during progressive handgrip exercise in the elderly through a nitric oxide-mediated mechanism.
abstract: The proposed mechanistic link between the age-related attenuation in vascular function and free radicals is an attractive hypothesis; however, direct evidence of free radical attenuation and a concomitant improvement in vascular function in the elderly is lacking. Therefore, this study sought to test the hypothesis that ascorbic acid (AA), administered intra-arterially during progressive handgrip exercise, improves brachial artery (BA) vasodilation in a nitric oxide (NO)-dependent manner, by mitigating free radical production. BA vasodilation (Doppler ultrasound) and free radical outflow [electron paramagnetic resonance (EPR) spectroscopy] were measured in seven healthy older adults (69 ± 2 yr) during handgrip exercise at 3, 6, 9, and 12 kg (∼13-52% of maximal voluntary contraction) during the control condition and nitric oxide synthase (NOS) inhibition via N(G)-monomethyl-L-arginine (L-NMMA), AA, and coinfusion of l-NMMA + AA. Baseline BA diameter was not altered by any of the treatments, while L-NMMA and L-NMMA + AA diminished baseline BA blood flow and shear rate. AA improved BA dilation compared with control at 9 kg (control: 6.5 ± 2.2%, AA: 10.9 ± 2.5%, P = 0.01) and 12 kg (control: 9.5 ± 2.7%, AA: 15.9 ± 3.7%, P < 0.01). NOS inhibition blunted BA vasodilation compared with control and when combined with AA eliminated the AA-induced improvement in BA vasodilation. Free radical outflow increased with exercise intensity but, interestingly, was not attenuated by AA. Collectively, these results indicate that AA improves BA vasodilation in the elderly during handgrip exercise through an NO-dependent mechanism; however, this improvement appears not to be the direct consequence of attenuated free radical outflow from the forearm.
authors.affiliation: Geriatric Research, Education, and Clinical Center, George E. Whalen Department of Veterans Affairs Medical Center, Salt Lake City, Utah; Division of Geriatrics, Department of Internal Medicine, University of Utah, Salt Lake City, Utah; joel.trinity@utah.edu.
authors.forename: Joel D
authors.initials: JD
authors.lastname: Trinity
authors.affiliation: Geriatric Research, Education, and Clinical Center, George E. Whalen Department of Veterans Affairs Medical Center, Salt Lake City, Utah; Division of Geriatrics, Department of Internal Medicine, University of Utah, Salt Lake City, Utah; Department of Exercise and Sport Science, University of Utah, Salt Lake City, Utah; and.
authors.forename: D Walter
authors.initials: DW
authors.lastname: Wray
authors.affiliation: Geriatric Research, Education, and Clinical Center, George E. Whalen Department of Veterans Affairs Medical Center, Salt Lake City, Utah; Division of Geriatrics, Department of Internal Medicine, University of Utah, Salt Lake City, Utah;
authors.forename: Melissa A H
authors.initials: MA
authors.lastname: Witman
authors.affiliation: Division of Geriatrics, Department of Internal Medicine, 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; and.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Barrett-O'Keefe
authors.affiliation: Geriatric Research, Education, and Clinical Center, George E. Whalen Department of Veterans Affairs Medical Center, Salt Lake City, Utah; Division of Geriatrics, Department of Internal Medicine, University of Utah, Salt Lake City, Utah;
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Ives
authors.affiliation: Geriatric Research, Education, and Clinical Center, George E. Whalen Department of Veterans Affairs Medical Center, Salt Lake City, Utah; Pulmonary Division, Department of Internal Medicine, University of Utah, Salt Lake City, Utah.
authors.forename: Jamie D
authors.initials: JD
authors.lastname: Conklin
authors.affiliation: Division of Geriatrics, Department of Internal Medicine, University of Utah, Salt Lake City, Utah;
authors.forename: Van
authors.initials: V
authors.lastname: Reese
authors.affiliation: Division of Geriatrics, Department of Internal Medicine, University of Utah, Salt Lake City, Utah;
authors.forename: Jia
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Geriatric Research, Education, and Clinical Center, George E. Whalen Department of Veterans Affairs Medical Center, Salt Lake City, Utah; Division of Geriatrics, Department of Internal Medicine, University of Utah, Salt Lake City, Utah; Department of Exercise and Sport Science, University of Utah, Salt Lake City, Utah; and.
authors.forename: Russell S
authors.initials: RS
authors.lastname: Richardson
mesh_terms: D000368:Aged; D001205:Ascorbic Acid / Q000494:pharmacology*; D001916:Brachial Artery / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015444:Exercise; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D018737:Hand Strength; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D012039:Regional Blood Flow / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D005609:Free Radicals; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D001205:Ascorbic Acid
keywords: aging; endothelium; l-NMMA; vascular function