Intradermal administration of ATP does not mitigate tyramine-stimulated vasoconstriction in human skin

Jonathan E. Wingo, R. Matthew Brothers, Juan Del Coso, Craig G. Crandall

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Cutaneous vasodilation associated with whole-body heat stress occurs via withdrawal of adrenergic vasoconstriction and engagement of cholinergic "active" vasodilation, the latter of which attenuates cutaneous vasoconstrictor responsiveness. However, the precise neurotransmitter(s) responsible for this sympatholytic-like effect remain unknown. In skeletal muscle, ATP inhibits adrenergically mediated vasoconstriction. ATP also may be responsible for attenuating cutaneous vasoconstriction since it is coreleased from cholinergic neurons. The effect of ATP on cutaneous vasoconstrictor responsiveness, however, has not been investigated. Accordingly, this study tested the hypothesis that ATP inhibits adrenergically mediated cutaneous vasoconstriction. To accomplish this objective, four microdialysis probes were inserted in dorsal forearm skin of 11 healthy individuals (mean ± SD; 35 ± 11 years). Local temperature at each site was clamped at 34°C throughout the protocol. Skin blood flow was indexed by laser-Doppler flowmetry and was used to calculate cutaneous vascular conductance (CVC; laser-Doppler-derived flux/mean arterial pressure), which was normalized to peak CVC achieved with sodium nitroprusside infusion combined with local skin heating to ∼42°C. Two membranes were perfused with 30 mM ATP, while the other two membranes were flow matched via administration of 2.8 mM adenosine to serve as control sites. After achieving stable baselines, 1x10-4 M tyramine was administered at all sites, while ATP and adenosine continued to be infused at their respective sites. ATP and adenosine infusion increased CVC from baseline by 35 ± 26% CVCpeak units and by 36 ± 15% CVCpeak units, respectively (P = 0.75). Tyramine decreased CVC similarly (by about one-third) at all sites (P < 0.001 for main effect and P = 0.32 for interaction). These findings indicate that unlike in skeletal muscle, ATP does not attenuate tyramine-stimulated vasoconstriction in human skin.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume298
Issue number5
DOIs
StatePublished - May 2010

Fingerprint

Tyramine
Vasoconstriction
Adenosine Triphosphate
Skin
Adenosine
Vasoconstrictor Agents
Vasodilation
Skeletal Muscle
Sympatholytics
Laser-Doppler Flowmetry
Cholinergic Neurons
Membranes
Microdialysis
Nitroprusside
Forearm
Adrenergic Agents
Heating
Cholinergic Agents
Neurotransmitter Agents
Blood Vessels

Keywords

  • Cutaneous vasodilation
  • Laser-doppler flowmetry
  • Skin blood flow
  • Thermoregulation

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Intradermal administration of ATP does not mitigate tyramine-stimulated vasoconstriction in human skin. / Wingo, Jonathan E.; Matthew Brothers, R.; Del Coso, Juan; Crandall, Craig G.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 298, No. 5, 05.2010.

Research output: Contribution to journalArticle

@article{4b4f5951c7de44d9a26ba7cd9b108396,
title = "Intradermal administration of ATP does not mitigate tyramine-stimulated vasoconstriction in human skin",
abstract = "Cutaneous vasodilation associated with whole-body heat stress occurs via withdrawal of adrenergic vasoconstriction and engagement of cholinergic {"}active{"} vasodilation, the latter of which attenuates cutaneous vasoconstrictor responsiveness. However, the precise neurotransmitter(s) responsible for this sympatholytic-like effect remain unknown. In skeletal muscle, ATP inhibits adrenergically mediated vasoconstriction. ATP also may be responsible for attenuating cutaneous vasoconstriction since it is coreleased from cholinergic neurons. The effect of ATP on cutaneous vasoconstrictor responsiveness, however, has not been investigated. Accordingly, this study tested the hypothesis that ATP inhibits adrenergically mediated cutaneous vasoconstriction. To accomplish this objective, four microdialysis probes were inserted in dorsal forearm skin of 11 healthy individuals (mean ± SD; 35 ± 11 years). Local temperature at each site was clamped at 34°C throughout the protocol. Skin blood flow was indexed by laser-Doppler flowmetry and was used to calculate cutaneous vascular conductance (CVC; laser-Doppler-derived flux/mean arterial pressure), which was normalized to peak CVC achieved with sodium nitroprusside infusion combined with local skin heating to ∼42°C. Two membranes were perfused with 30 mM ATP, while the other two membranes were flow matched via administration of 2.8 mM adenosine to serve as control sites. After achieving stable baselines, 1x10-4 M tyramine was administered at all sites, while ATP and adenosine continued to be infused at their respective sites. ATP and adenosine infusion increased CVC from baseline by 35 ± 26{\%} CVCpeak units and by 36 ± 15{\%} CVCpeak units, respectively (P = 0.75). Tyramine decreased CVC similarly (by about one-third) at all sites (P < 0.001 for main effect and P = 0.32 for interaction). These findings indicate that unlike in skeletal muscle, ATP does not attenuate tyramine-stimulated vasoconstriction in human skin.",
keywords = "Cutaneous vasodilation, Laser-doppler flowmetry, Skin blood flow, Thermoregulation",
author = "Wingo, {Jonathan E.} and {Matthew Brothers}, R. and {Del Coso}, Juan and Crandall, {Craig G.}",
year = "2010",
month = "5",
doi = "10.1152/ajpregu.00846.2009",
language = "English (US)",
volume = "298",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "5",

}

TY - JOUR

T1 - Intradermal administration of ATP does not mitigate tyramine-stimulated vasoconstriction in human skin

AU - Wingo, Jonathan E.

AU - Matthew Brothers, R.

AU - Del Coso, Juan

AU - Crandall, Craig G.

PY - 2010/5

Y1 - 2010/5

N2 - Cutaneous vasodilation associated with whole-body heat stress occurs via withdrawal of adrenergic vasoconstriction and engagement of cholinergic "active" vasodilation, the latter of which attenuates cutaneous vasoconstrictor responsiveness. However, the precise neurotransmitter(s) responsible for this sympatholytic-like effect remain unknown. In skeletal muscle, ATP inhibits adrenergically mediated vasoconstriction. ATP also may be responsible for attenuating cutaneous vasoconstriction since it is coreleased from cholinergic neurons. The effect of ATP on cutaneous vasoconstrictor responsiveness, however, has not been investigated. Accordingly, this study tested the hypothesis that ATP inhibits adrenergically mediated cutaneous vasoconstriction. To accomplish this objective, four microdialysis probes were inserted in dorsal forearm skin of 11 healthy individuals (mean ± SD; 35 ± 11 years). Local temperature at each site was clamped at 34°C throughout the protocol. Skin blood flow was indexed by laser-Doppler flowmetry and was used to calculate cutaneous vascular conductance (CVC; laser-Doppler-derived flux/mean arterial pressure), which was normalized to peak CVC achieved with sodium nitroprusside infusion combined with local skin heating to ∼42°C. Two membranes were perfused with 30 mM ATP, while the other two membranes were flow matched via administration of 2.8 mM adenosine to serve as control sites. After achieving stable baselines, 1x10-4 M tyramine was administered at all sites, while ATP and adenosine continued to be infused at their respective sites. ATP and adenosine infusion increased CVC from baseline by 35 ± 26% CVCpeak units and by 36 ± 15% CVCpeak units, respectively (P = 0.75). Tyramine decreased CVC similarly (by about one-third) at all sites (P < 0.001 for main effect and P = 0.32 for interaction). These findings indicate that unlike in skeletal muscle, ATP does not attenuate tyramine-stimulated vasoconstriction in human skin.

AB - Cutaneous vasodilation associated with whole-body heat stress occurs via withdrawal of adrenergic vasoconstriction and engagement of cholinergic "active" vasodilation, the latter of which attenuates cutaneous vasoconstrictor responsiveness. However, the precise neurotransmitter(s) responsible for this sympatholytic-like effect remain unknown. In skeletal muscle, ATP inhibits adrenergically mediated vasoconstriction. ATP also may be responsible for attenuating cutaneous vasoconstriction since it is coreleased from cholinergic neurons. The effect of ATP on cutaneous vasoconstrictor responsiveness, however, has not been investigated. Accordingly, this study tested the hypothesis that ATP inhibits adrenergically mediated cutaneous vasoconstriction. To accomplish this objective, four microdialysis probes were inserted in dorsal forearm skin of 11 healthy individuals (mean ± SD; 35 ± 11 years). Local temperature at each site was clamped at 34°C throughout the protocol. Skin blood flow was indexed by laser-Doppler flowmetry and was used to calculate cutaneous vascular conductance (CVC; laser-Doppler-derived flux/mean arterial pressure), which was normalized to peak CVC achieved with sodium nitroprusside infusion combined with local skin heating to ∼42°C. Two membranes were perfused with 30 mM ATP, while the other two membranes were flow matched via administration of 2.8 mM adenosine to serve as control sites. After achieving stable baselines, 1x10-4 M tyramine was administered at all sites, while ATP and adenosine continued to be infused at their respective sites. ATP and adenosine infusion increased CVC from baseline by 35 ± 26% CVCpeak units and by 36 ± 15% CVCpeak units, respectively (P = 0.75). Tyramine decreased CVC similarly (by about one-third) at all sites (P < 0.001 for main effect and P = 0.32 for interaction). These findings indicate that unlike in skeletal muscle, ATP does not attenuate tyramine-stimulated vasoconstriction in human skin.

KW - Cutaneous vasodilation

KW - Laser-doppler flowmetry

KW - Skin blood flow

KW - Thermoregulation

UR - http://www.scopus.com/inward/record.url?scp=77951751835&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77951751835&partnerID=8YFLogxK

U2 - 10.1152/ajpregu.00846.2009

DO - 10.1152/ajpregu.00846.2009

M3 - Article

VL - 298

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 5

ER -