Effect of elevated local temperature on cutaneous vasoconstrictor responsiveness in humans

Jonathan E. Wingo, David A. Low, David M. Keller, R. Matthew Brothers, Manabu Shibasaki, Craig G. Crandall

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Cutaneous vascular conductance (CVC) increases in response to local skin heating. Although attenuation of vasoconstrictor responsiveness due to local heating has been demonstrated, the mechanism( s) responsible for this attenuation remains unclear. Nitric oxide has been shown to at least partially contribute to this response, but other mechanisms also may be involved. The purpose of this study was to test the hypothesis that local heating diminishes cutaneous vasoconstrictor responsiveness through a nitric oxide-independent mechanism by altering postsynaptic reactivity to norepinephrine. A follow-up protocol tested the hypothesis that local heating attenuates the presynaptic release of neurotransmitters that cause vasoconstriction, also via non-nitric oxide mechanisms. In protocol I, CVC was assessed in eight subjects during administration of increasing doses of norepinephrine (via intradermal microdialysis) at adjacent sites separately heated to 34°C and 40°C. In protocol II, which was identical to, but separate from, protocol I, CVC was assessed in seven subjects during administration of increasing doses of tyramine, which causes release of neurotransmitters from adrenergic nerves. At each site for both protocols, nitric oxide synthesis was inhibited (via microdialysis administration of NG-nitro-L-arginine methyl ester) and flow was matched (via microdialysis administration of adenosine); therefore, temperature was the only variable that differed between the sites. For both protocols, nonlinear regression analysis revealed no difference (P > 0.05) in the effective drug concentration causing 50% of the vasoconstrictor response. Minimum CVC [6.3 ± 2.0 and 9.0 ± 4.0% of peak CVC (mean ± SD) for protocol I and 19.3 ± 9.3 and 20.5 ± 11.9% of peak CVC for protocol II at 34°C and 40°C sites, respectively] was not different between sites. Independent of nitric oxide, local skin heating to 40°C does not attenuate adrenergically mediated cutaneous vasoconstriction through pre- or postsynaptic mechanisms.

Original languageEnglish (US)
Pages (from-to)571-575
Number of pages5
JournalJournal of applied physiology
Issue number2
StatePublished - Feb 2009


  • Microdialysis
  • Nitric oxide
  • Norepinephrine
  • Skin temperature
  • Tyramine

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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