title: Impact of age on the vasodilatory function of human skeletal muscle feed arteries.
abstract: Although advancing age is often associated with attenuated skeletal muscle blood flow and skeletal muscle feed arteries (SMFAs) have been recognized to play a regulatory role in the vasculature, little is known about the impact of age on the vasodilatory capacity of human SMFAs. Therefore, endothelium-dependent and -independent vasodilation were assessed in SMFAs (diameter: 544 ± 63 μm) obtained from 24 (equally represented) young (33 ± 2 yr) and old (71 ± 2 yr) subjects in response to three stimuli: 1) flow-induced shear stress, 2) ACh, and 3) sodium nitropusside (SNP). Both assessments of endothelium-dependent vasodilation, flow (young subjects: 68 ± 1% and old subjects: 32 ± 7%) and ACh (young subjects: 92 ± 3% and old subjects: 73 ± 4%), were significantly blunted (P < 0.05) in SMFAs of old compared with young subjects, with no such age-related differences in endothelium-independent vasodilation (SNP). In response to an increase in flow-induced shear stress, vasodilation kinetics (time constant to reach 63% of the amplitude of the response: 55 ± 1 s in young subjects and 92 ± 7 s in old subjects) and endothelial nitric oxide synthase (eNOS) activation (phospho-eNOS(s1177)/total eNOS: 1.0 ± 0.1 in young subjects and 0.2 ± 0.1 in old subjects) were also significantly attenuated in old compared with young subjects (P < 0.05). Furthermore, the vessel superoxide concentration was greater in old subjects (old subjects: 3.9 ± 1.0 area under curve/mg and young subjects: 1.7 ± 0.1 area under the curve/mg, P < 0.05). These findings reveal that the endothelium-dependent vasodilatory capacity, including vasodilation kinetics but not smooth muscle function, of human SMFAs is blunted with age and may be due to free radicals. Given the potential regulatory role of SMFAs in skeletal muscle blood flow, these findings may explain, at least in part, the often observed attenuated perfusion of skeletal muscle with advancing age that may contribute to exercise intolerance in the elderly.
authors.affiliation: Geriatric Research, Education, and Clinical Center, George E. Whalen Veterans Affairs Medical Center, Salt Lake City, Utah; Department of Exercise and Sport Science, University of Utah, Salt Lake City, Utah;
authors.forename: Song-Young
authors.initials: SY
authors.lastname: Park
authors.affiliation: Geriatric Research, Education, and Clinical Center, George E. Whalen Veterans Affairs Medical Center, Salt Lake City, Utah; Health and Exercise Sciences Department, Skidmore College, Saratoga Springs, New York; and.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Ives
authors.affiliation: Geriatric Research, Education, and Clinical Center, George E. Whalen Veterans Affairs Medical Center, Salt Lake City, Utah; Department of Exercise and Sport Science, University of Utah, Salt Lake City, Utah;
authors.forename: Jayson R
authors.initials: JR
authors.lastname: Gifford
authors.affiliation: Department of Surgery, Huntsman Cancer Hospital, University of Utah, Salt Lake City, Utah;
authors.forename: Robert H I
authors.initials: RH
authors.lastname: Andtbacka
authors.affiliation: Department of Surgery, Huntsman Cancer Hospital, University of Utah, Salt Lake City, Utah;
authors.forename: John R
authors.initials: JR
authors.lastname: Hyngstrom
authors.affiliation: Geriatric Research, Education, and Clinical Center, George E. Whalen Veterans Affairs Medical Center, Salt Lake City, Utah; 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: Geriatric Research, Education, and Clinical Center, George E. Whalen Veterans Affairs Medical Center, Salt Lake City, Utah; 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: Division of Endocrinology, Metabolism, and Diabetes, School of Medicine, University of Utah, Salt Lake City, Utah.
authors.forename: Leena P
authors.initials: LP
authors.lastname: Bharath
authors.affiliation: Department of Exercise and Sport Science, University of Utah, Salt Lake City, Utah; Division of Endocrinology, Metabolism, and Diabetes, School of Medicine, University of Utah, Salt Lake City, Utah.
authors.forename: John D
authors.initials: JD
authors.lastname: Symons
authors.affiliation: Geriatric Research, Education, and Clinical Center, George E. Whalen 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; r.richardson@hsc.utah.edu.
authors.forename: Russell S
authors.initials: RS
authors.lastname: Richardson
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D001158:Arteries / Q000201:enzymology / Q000254:growth & development* / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000201:enzymology; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D012039:Regional Blood Flow / Q000502:physiology; D013312:Stress, Physiological / Q000502:physiology; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D005609:Free Radicals; D014665:Vasodilator Agents; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III
keywords: aging; endothelium-dependent vasodilation; human skeletal muscle feed artery