Antagonism of soluble guanylyl cyclase attenuates cutaneous vasodilation during whole body heat stress and local warming in humans

Dean L. Kellogg, Joan L. Zhao, Yubo Wu, John M. Johnson

Research output: Contribution to journalArticle

20 Scopus citations

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% CVCmax; Ringer, 17 ± 6% CVCmax; P ± 0.05]. During heat stress, ODQ attenuated CVC increases (ODQ, 54 ± 4% CVCmax; DMSO, 64 ± 4% CVC max; Ringer, 63 ± 4% CVCmax; 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% CVCmax; DMSO, 18 ± 4% CVCmax; Ringer, 18 ± 3% CVCmax; P > 0.05). ODQ attenuated CVC increases at 41°C local temperature (ODQ, 54 ± 5% CVCmax; DMSO, 86 ± 4% CVCmax; Ringer, 90 ± 2% CVCmax; 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.

Original languageEnglish (US)
Pages (from-to)1406-1413
Number of pages8
JournalJournal of applied physiology
Volume110
Issue number5
DOIs
StatePublished - May 1 2011

Keywords

  • Guanosine 3=,5=-cyclic monophosphate
  • Microdialysis
  • Nitric oxide
  • Skin
  • Thermoregulation

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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