title: Endogenous endothelin-1 and femoral artery shear rate: impact of age and implications for atherosclerosis.
abstract: BACKGROUND
  Both altered shear rate and endothelin-1 (ET-1) are associated with the age-related development of atherosclerosis. However, the role of ET-1, a potent endogenous vasoconstrictor, in altering shear rate in humans, especially in the atherosclerotic-prone vasculature of the leg, is unknown. Therefore, this study examined the contribution of ET-1 to the age-related alterations in common femoral artery (CFA) shear rate.
  
  
  METHODS
  BQ-123, a specific endothelin type A (ET(A)) receptor antagonist, was infused into the CFA, and diameter and blood velocity were measured by Doppler ultrasound in young (n = 8, 24 ± 2 years) and old (n = 9, 70 ± 2 years) study participants.
  
  
  CONCLUSIONS
  The old had greater intima-media thickening in the CFA, indicative of a preatherogenic phenotype. Prior to infusion, the old study participants exhibited reduced mean shear rate (27 ± 3/s) compared with the young study participants (62 ± 9/s). This difference was likely driven by attenuated antegrade shear rate in the old as retrograde shear rate was similar in the young and old. Inhibition of ETA receptors, by BQ-123, increased leg blood flow in the old, but not in the young, abolishing age-related differences. Older study participants had a larger CFA (young: 0.82 ± 0.03 cm, old: 0.99 ± 0.03 cm) in which BQ-123 induced significant vasodilation (5.1 ± 1.0%), but had no such effect in the young (-0.8 ± 0.8%). Interestingly, despite the age-specific, BQ-123-induced increase in leg blood flow and CFA diameter, shear rate patterns remained largely unchanged. Therefore, ET-1, acting through the ETA receptors, exerts a powerful age-specific vasoconstriction. However, removal of this vasoconstrictor stimulus does not augment mean shear rate in the old.
authors.affiliation: aDepartment of Internal Medicine, University of UtahbGeriatric Research, Education, and Clinical Center, Salt Lake City Veterans Affairs Medical CentercUniversity of Utah Center on AgingdDepartment of Exercise and Sport ScienceeDepartment of Anesthesiology, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Joel D
authors.initials: JD
authors.lastname: Trinity
authors.forename: Zachary
authors.initials: Z
authors.lastname: Barrett-O'Keefe
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Ives
authors.forename: Garrett
authors.initials: G
authors.lastname: Morgan
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Rossman
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Donato
authors.forename: Sean
authors.initials: S
authors.lastname: Runnels
authors.forename: David E
authors.initials: DE
authors.lastname: Morgan
authors.forename: Benjamin S
authors.initials: BS
authors.lastname: Gmelch
authors.forename: Amber D
authors.initials: AD
authors.lastname: Bledsoe
authors.forename: Russell S
authors.initials: RS
authors.lastname: Richardson
authors.forename: D Walter
authors.initials: DW
authors.lastname: Wray
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D050197:Atherosclerosis / Q000503:physiopathology*; D001783:Blood Flow Velocity / Q000187:drug effects; D065128:Endothelin Receptor Antagonists / Q000494:pharmacology; D019332:Endothelin-1 / Q000502:physiology*; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000187:drug effects; D005263:Femoral Artery / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D010456:Peptides, Cyclic / Q000494:pharmacology; D018608:Ultrasonography, Doppler; D014664:Vasodilation / Q000187:drug effects; D055815:Young Adult
chemical_list: D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D010456:Peptides, Cyclic; C072247:cyclo(Trp-Asp-Pro-Val-Leu)