title: Antagonism of soluble guanylyl cyclase attenuates cutaneous vasodilation during whole body heat stress and local warming in humans.
abstract: We hypothesized that nitric oxide activation of soluble guanylyl cyclase (sGC) participates in cutaneous vasodilation during whole body heat stress and local skin warming. We examined the effects of the sGC inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), on reflex skin blood flow responses to whole body heat stress and on nonreflex responses to increased local skin temperature. Blood flow was monitored by laser-Doppler flowmetry, and blood pressure by Finapres to calculate cutaneous vascular conductance (CVC). Intradermal microdialysis was used to treat one site with 1 mM ODQ in 2% DMSO and Ringer, a second site with 2% DMSO in Ringer, and a third site received Ringer. In protocol 1, after a period of normothermia, whole body heat stress was induced. In protocol 2, local heating units warmed local skin temperature from 34 to 41°C to cause local vasodilation. In protocol 1, in normothermia, CVC did not differ among sites [ODQ, 15 ± 3% maximum CVC (CVC(max)); DMSO, 14 ± 3% CVC(max); Ringer, 17 ± 6% CVC(max); P > 0.05]. During heat stress, ODQ attenuated CVC increases (ODQ, 54 ± 4% CVC(max); DMSO, 64 ± 4% CVC(max); Ringer, 63 ± 4% CVC(max); P < 0.05, ODQ vs. DMSO or Ringer). In protocol 2, at 34°C local temperature, CVC did not differ among sites (ODQ, 17 ± 2% CVC(max); DMSO, 18 ± 4% CVC(max); Ringer, 18 ± 3% CVC(max); P > 0.05). ODQ attenuated CVC increases at 41°C local temperature (ODQ, 54 ± 5% CVC(max); DMSO, 86 ± 4% CVC(max); Ringer, 90 ± 2% CVC(max); P < 0.05 ODQ vs. DMSO or Ringer). sGC participates in neurogenic active vasodilation during heat stress and in the local response to direct skin warming.
authors.affiliation: Geriatric Research, Education, and Clinical Center, Department of Veterans Affairs, South Texas Veterans Health Care System, Audie L. Murphy Memorial Veterans Hospital Division, San Antonio, Texas, USA. kelloggd@uthscsa.edu
authors.forename: Dean L
authors.initials: DL
authors.lastname: Kellogg
authors.forename: Joan L
authors.initials: JL
authors.lastname: Zhao
authors.forename: Yubo
authors.initials: Y
authors.lastname: Wu
authors.forename: John M
authors.initials: JM
authors.lastname: Johnson
mesh_terms: D000328:Adult; D001783:Blood Flow Velocity / Q000502:physiology; D001833:Body Temperature Regulation / Q000502:physiology*; D005260:Female; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D018869:Heat-Shock Response / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*; D012867:Skin / Q000098:blood supply; D012881:Skin Temperature / Q000187:drug effects / Q000502:physiology*; D012995:Solubility; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D009569:Nitric Oxide; D006162:Guanylate Cyclase