title: Cutaneous blood flow during intradermal NO administration in young and older adults: roles for calcium-activated potassium channels and cyclooxygenase?
abstract: Nitric oxide (NO) increases cutaneous blood flow; however, the underpinning mechanism(s) remains to be elucidated. We hypothesized that the cutaneous blood flow response during intradermal administration of sodium nitroprusside (SNP, a NO donor) is regulated by calcium-activated potassium (KCa) channels and cyclooxygenase (COX) in young adults. We also hypothesized that these contributions are diminished in older adults given that aging can downregulate KCa channels and reduce COX-derived vasodilator prostanoids. In 10 young (23 ± 5 yr) and 10 older (54 ± 4 yr) adults, cutaneous vascular conductance (CVC) was measured at four forearm skin sites infused with 1) Ringer (Control), 2) 50 mM tetraethylammonium (TEA), a nonspecific KCa channel blocker, 3) 10 mM ketorolac, a nonspecific COX inhibitor, or 4) 50 mM TEA + 10 mM ketorolac via intradermal microdialysis. All skin sites were coinfused with incremental doses of SNP (0.005, 0.05, 0.5, 5, and 50 mM each for 25 min). During SNP administration, CVC was similar at the ketorolac site (0.005-50 mM, all P > 0.05) relative to Control, but lower at the TEA and TEA + ketorolac sites (0.005-0.05 mM, all P < 0.05) in young adults. In older adults, ketorolac increased CVC relative to Control during 0.005-0.05 mM SNP administration (all P < 0.05), but this increase was not observed when TEA was coadministered (all P > 0.05). Furthermore, TEA alone did not modulate CVC during any concentration of SNP administration in older adults (all P > 0.05). We show that during low-dose NO administration (e.g., 0.005-0.05 mM), KCa channels contribute to cutaneous blood flow regulation in young adults; however, in older adults, COX inhibition increases cutaneous blood flow through a KCa channel-dependent mechanism.
authors.affiliation: Human and Environmental Physiology Research Unit, University of Ottawa, Ottawa, Canada;
authors.forename: Naoto
authors.initials: N
authors.lastname: Fujii
authors.affiliation: Human and Environmental Physiology Research Unit, University of Ottawa, Ottawa, Canada;
authors.forename: Robert D
authors.initials: RD
authors.lastname: Meade
authors.affiliation: Department of Human Physiology, The University of Oregon, Eugene, Oregon;
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Minson
authors.affiliation: Department of Human Physiology, The University of Oregon, Eugene, Oregon;
authors.forename: Vienna E
authors.initials: VE
authors.lastname: Brunt
authors.affiliation: Faculty of Physical Activity Sciences, University of Sherbrooke, Sherbrooke, Canada; and.
authors.forename: Pierre
authors.initials: P
authors.lastname: Boulay
authors.affiliation: Departments of Medicine, Cardiac Sciences and Community Health Sciences, Faculties of Medicine and Kinesiology, University of Calgary, Calgary, Canada.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Sigal
authors.affiliation: Human and Environmental Physiology Research Unit, University of Ottawa, Ottawa, Canada; gkenny@uottawa.ca.
authors.forename: Glen P
authors.initials: GP
authors.lastname: Kenny
mesh_terms: D000328:Adult; D000375:Aging / Q000187:drug effects / Q000502:physiology*; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000008:administration & dosage*; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000378:metabolism*; D012879:Skin Physiological Phenomena / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000008:administration & dosage
chemical_list: D024681:Potassium Channels, Calcium-Activated; D014665:Vasodilator Agents; D009569:Nitric Oxide; D011451:Prostaglandin-Endoperoxide Synthases
keywords: aging; endothelial cell; endothelium-derived hyperpolarizing factors; microcirculation; nitric oxide synthase; prostanoids; smooth muscle cell; soluble guanylyl cyclase