title: Endothelin-A-mediated vasoconstriction during exercise with advancing age.
abstract: The endothelin-1 vasoconstrictor pathway contributes to age-related elevations in resting peripheral vascular tone primarily through activation of the endothelin subtype A (ET(A)) receptor. However, the regulatory influence of ET(A)-mediated vasoconstriction during exercise in the elderly is unknown. Thus, in 17 healthy volunteers (n = 8 young, 24±2 years; n = 9 old, 70±2 years), we examined leg blood flow, mean arterial pressure, leg arterial-venous oxygen (O2) difference, and leg O2 consumption (VO2) at rest and during knee-extensor exercise before and after intra-arterial administration of the ET(A) antagonist BQ-123. During exercise, BQ-123 administration increased leg blood flow to a greater degree in the old (+29±5 mL/min/W) compared with the young (+16±3 mL/min/W). The increase in leg blood flow with BQ-123 was accompanied by an increase in leg VO2 in both groups, suggesting a reduced efficiency following ET(A) receptor blockade. Together, these findings have identified an age-related increase in ET(A)-mediated vasoconstrictor activity that persists during exercise, suggesting an important role of this pathway in the regulation of exercising skeletal muscle blood flow and maintenance of arterial blood pressure in the elderly.
authors.affiliation: Department of Exercise and Sport Science, University of Utah, Salt Lake City. Geriatric Research, Education, and Clinical Center, Salt Lake City Veterans Affairs Medical Center, Utah.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Barrett-O'Keefe
authors.affiliation: Geriatric Research, Education, and Clinical Center, Salt Lake City Veterans Affairs Medical Center, Utah. Department of Internal Medicine, University of Utah, Salt Lake City.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Ives
authors.affiliation: Geriatric Research, Education, and Clinical Center, Salt Lake City Veterans Affairs Medical Center, Utah. Department of Internal Medicine, University of Utah, Salt Lake City.
authors.forename: Joel D
authors.initials: JD
authors.lastname: Trinity
authors.affiliation: Geriatric Research, Education, and Clinical Center, Salt Lake City Veterans Affairs Medical Center, Utah.
authors.forename: Garrett
authors.initials: G
authors.lastname: Morgan
authors.affiliation: Department of Exercise and Sport Science, University of Utah, Salt Lake City. Geriatric Research, Education, and Clinical Center, Salt Lake City Veterans Affairs Medical Center, Utah.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Rossman
authors.affiliation: Department of Exercise and Sport Science, University of Utah, Salt Lake City. Geriatric Research, Education, and Clinical Center, Salt Lake City Veterans Affairs Medical Center, Utah. Department of Internal Medicine, University of Utah, Salt Lake City. University of Utah Center on Aging, Salt Lake City.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Donato
authors.affiliation: Department of Anesthesiology, University of Utah, Salt Lake City.
authors.forename: Sean
authors.initials: S
authors.lastname: Runnels
authors.affiliation: Department of Anesthesiology, University of Utah, Salt Lake City.
authors.forename: David E
authors.initials: DE
authors.lastname: Morgan
authors.affiliation: Department of Anesthesiology, University of Utah, Salt Lake City.
authors.forename: Benjamin S
authors.initials: BS
authors.lastname: Gmelch
authors.affiliation: Department of Anesthesiology, University of Utah, Salt Lake City.
authors.forename: Amber D
authors.initials: AD
authors.lastname: Bledsoe
authors.affiliation: Department of Exercise and Sport Science, University of Utah, Salt Lake City. Geriatric Research, Education, and Clinical Center, Salt Lake City Veterans Affairs Medical Center, Utah. Department of Internal Medicine, University of Utah, Salt Lake City. University of Utah Center on Aging, Salt Lake City.
authors.forename: Russell S
authors.initials: RS
authors.lastname: Richardson
authors.affiliation: Department of Exercise and Sport Science, University of Utah, Salt Lake City. Geriatric Research, Education, and Clinical Center, Salt Lake City Veterans Affairs Medical Center, Utah. Department of Internal Medicine, University of Utah, Salt Lake City. University of Utah Center on Aging, Salt Lake City. walter.wray@hsc.utah.edu.
authors.forename: D Walter
authors.initials: DW
authors.lastname: Wray
mesh_terms: D000368:Aged; D000375:Aging / Q000502:physiology*; D062186:Arterial Pressure / Q000502:physiology; D065128:Endothelin Receptor Antagonists / Q000008:administration & dosage*; D015444:Exercise / Q000502:physiology*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007866:Leg / Q000098:blood supply; D008055:Lipids / Q000097:blood; D008297:Male; D010101:Oxygen Consumption / Q000502:physiology; D010456:Peptides, Cyclic / Q000008:administration & dosage*; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology*; D055815:Young Adult
chemical_list: D065128:Endothelin Receptor Antagonists; D008055:Lipids; D010456:Peptides, Cyclic; C072247:cyclo(Trp-Asp-Pro-Val-Leu)
keywords: Aging.; Arterial; Blood; Endothelin-1; Exercise; blood p; flow; ressure