title: Impact of age and body position on the contribution of nitric oxide to femoral artery shear rate: implications for atherosclerosis.
abstract: Reduced shear stress and augmented oscillatory shear rate are associated with the proatherogenic phenotype observed with aging. To date, mechanisms contributing to the age-related alterations in shear rate in humans have only been examined in the conduit vessels of the arm. Therefore, this study sought to examine the contribution of nitric oxide (NO) bioavailability to age-related alterations in shear rate and the impact of common body positions (supine and seated) in the atherosclerotic-prone conduit artery of the leg. Inhibition of NO synthase (NOS) was accomplished by intra-arterial infusion of N(G)-monomethyl-l-arginine (L-NMMA), and common femoral artery diameter and blood velocity were measured by Doppler ultrasound in healthy young (n=8, 24±1 years) and old (n=8, 75±3 years) men. Old subjects exhibited reduced mean shear rate in the supine (18±3 s(-1)) and seated positions (17±3 s(-1)) compared with young subjects (supine: 42±6 s(-1); seated: 32±4 s(-1)). This reduced mean shear in the old was driven by attenuated antegrade shear as there were no differences in retrograde shear. Inhibition of NOS reduced antegrade shear in the young such that age-related differences were abolished. In contrast, NOS-induced reductions in retrograde shear rate were similar between groups. The seated position reduced mean shear rate in the young to that normally observed in old. Overall, this study reveals that age-related reductions in mean shear rate, assessed in the atherosclerotic-prone vasculature of the leg, are largely explained by reductions in antegrade shear as a result of reduced NO bioavailability in the elderly.
authors.affiliation: VA Medical Center, Bldg 2, RM 1D29A, 500 Foothill Dr, Salt Lake City, Utah 84148. joel.trinity@utah.edu.
authors.forename: Joel D
authors.initials: JD
authors.lastname: Trinity
authors.forename: H Jonathan
authors.initials: HJ
authors.lastname: Groot
authors.forename: Gwenael
authors.initials: G
authors.lastname: Layec
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Rossman
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Ives
authors.forename: Russell S
authors.initials: RS
authors.lastname: Richardson
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D050197:Atherosclerosis / Q000503:physiopathology*; D001682:Biological Availability; D005263:Femoral Artery / Q000000981:diagnostic imaging / Q000502:physiology*; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000187:drug effects; D010641:Phenotype; D011187:Posture / Q000502:physiology*; D012039:Regional Blood Flow / Q000502:physiology*; D033081:Shear Strength / Q000502:physiology*; D013314:Stress, Mechanical; D016683:Supine Position / Q000502:physiology; D018608:Ultrasonography, Doppler; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase
keywords: aging; atherosclerosis; nitric oxide; regional blood flow