title: Intradermal administration of endothelin-1 attenuates endothelium-dependent and -independent cutaneous vasodilation via Rho kinase in young adults.
abstract: We recently showed that intradermal administration of endothelin-1 diminished endothelium-dependent and -independent cutaneous vasodilation. We evaluated the hypothesis that Rho kinase may be a mediator of this response. We also sought to evaluate if endothelin-1 increases sweating. In 12 adults (25 ± 6 yr), we measured cutaneous vascular conductance (CVC) and sweating during 1) endothelium-dependent vasodilation induced via administration of incremental doses of methacholine (0.25, 5, 100, and 2,000 mM each for 25 min) and 2) endothelium-independent vasodilation induced via administration of 50 mM sodium nitroprusside (20-25 min). Responses were evaluated at four skin sites treated with either 1) lactated Ringer solution (Control), 2) 400 nM endothelin-1, 3) 3 mM HA-1077 (Rho kinase inhibitor), or 4) endothelin-1+HA-1077. Pharmacological agents were intradermally administered via microdialysis. Relative to the Control site, endothelin-1 attenuated endothelium-dependent vasodilation (CVC at 2,000 mM methacholine, 80 ± 10 vs. 56 ± 15%max, P < 0.01); however, this response was not detected when the Rho kinase inhibitor was simultaneously administered (CVC at 2,000 mM methacholine for Rho kinase inhibitor vs. endothelin-1 + Rho kinase inhibitor sites: 73 ± 9 vs. 72 ± 11%max, P > 0.05). Endothelium-independent vasodilation was attenuated by endothelin-1 compared with the Control site (CVC, 92 ± 13 vs. 70 ± 14%max, P < 0.01). However, in the presence of Rho kinase inhibition, endothelin-1 did not affect endothelium-independent vasodilation (CVC at Rho kinase inhibitor vs. endothelin-1+Rho kinase inhibitor sites: 81 ± 9 vs. 86 ± 10%max, P > 0.05). There was no between-site difference in sweating throughout (P > 0.05). We show that in young adults, Rho kinase is an important mediator of the endothelin-1-mediated attenuation of endothelium-dependent and -independent cutaneous vasodilation, and that endothelin-1 does not increase sweating.
authors.affiliation: Human and Environmental Physiology Research Unit, University of Ottawa, Ottawa, Canada; and.
authors.forename: Naoto
authors.initials: N
authors.lastname: Fujii
authors.affiliation: Laboratory for Exercise and Environmental Physiology, Faculty of Education, Niigata University, Niigata, Japan.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Amano
authors.affiliation: Human and Environmental Physiology Research Unit, University of Ottawa, Ottawa, Canada; and.
authors.forename: Lyra
authors.initials: L
authors.lastname: Halili
authors.affiliation: Human and Environmental Physiology Research Unit, University of Ottawa, Ottawa, Canada; and.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Louie
authors.affiliation: Human and Environmental Physiology Research Unit, University of Ottawa, Ottawa, Canada; and.
authors.forename: Sarah Y
authors.initials: SY
authors.lastname: Zhang
authors.affiliation: Human and Environmental Physiology Research Unit, University of Ottawa, Ottawa, Canada; and.
authors.forename: Brendan D
authors.initials: BD
authors.lastname: McNeely
authors.affiliation: Human and Environmental Physiology Research Unit, University of Ottawa, Ottawa, Canada; and gkenny@uottawa.ca.
authors.forename: Glen P
authors.initials: GP
authors.lastname: Kenny
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000008:administration & dosage*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D012867:Skin / Q000098:blood supply*; D013546:Sweating / Q000187:drug effects / Q000502:physiology*; D016896:Treatment Outcome; D014662:Vasoconstrictor Agents / Q000008:administration & dosage; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D019332:Endothelin-1; D014662:Vasoconstrictor Agents; D054460:rho-Associated Kinases
keywords: ROCK; endothelial cell; microcirculation; vascular smooth muscle cell