The involvement of norepinephrine, neuropeptide Y, and nitric oxide in the cutaneous vasodilator response to local heating in humans

Gary J. Hodges, Wojciech A. Kosiba, Kun Zhao, John M. Johnson

Research output: Contribution to journalArticlepeer-review

89 Scopus citations

Abstract

Presynaptic blockade of cutaneous vasoconstrictor nerves (VCN) abolishes the axon reflex (AR) during slow local heating (SLH) and reduces the vasodilator response. In a two-part study, forearm sites were instrumented with microdialysis fibers, local heaters, and laser-Doppler flow probes. Sites were locally heated from 33 to 40°C over 70 min. In part 1, we tested whether this effect of VCN acted via nitric oxide synthase (NOS). In five subjects, treatments were as follows: 1) untreated; 2) bretylium, preventing neurotransmitter release; 3) NG-nitro-L-arginine methyl ester (L-NAME) to inhibit NOS; and 4) combined bretylium + L-NAME. At treated sites, the AR was absent, and there was an attenuation of the ultimate vasodilation (P < 0.05), which was not different among those sites (P > 0.05). In part 2, we tested whether norepinephrine and/or neuropeptide Y is involved in the cutaneous vasodilator response to SLH. In seven subjects, treatments were as follows: 1) untreated; 2) propranolol and yohimbine to antagonize α-and β-receptors; 3) BIBP-3226 to antagonize Y1 receptors; and 4) combined propranolol + yohimbine + BIBP-3226. Treatment with propranolol + yohimbine or BIBP-3226 significantly increased the temperature at which AR occurred (n = 4) or abolished it (n = 3). The combination treatment consistently eliminated it. Importantly, ultimate vasodilation with SLH at the treated sites was significantly (P < 0.05) less than at the control. These data suggest that norepinephrine and neuropeptide Y are important in the initiation of the AR and for achieving a complete vasodilator response. Since VCN and NOS blockade in combination do not have an inhibition greater than either alone, these data suggest that VCN promote heat-induced vasodilation via a nitric oxide-dependent mechanism.

Original languageEnglish (US)
Pages (from-to)233-240
Number of pages8
JournalJournal of applied physiology
Volume105
Issue number1
DOIs
StatePublished - Jul 2008

Keywords

  • Axon reflex
  • BIBP-3226
  • Bretylium
  • Local control of blood flow
  • Yohimbine

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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