ATP Does Not Mitigate Adrenergically-Mediated Vasoconstriction in Human Skin

Abstract

Unknown factors associated with active cutaneous vasodilation have the capacity to attenuate adrenergically-mediated cutaneous vasoconstriction. Adenosine triphosphate (ATP) is reputedly co-released from sympathetic cholinergic nerves, which are the nerves responsible for cutaneous active vasodilation. In skeletal muscle, ATP inhibits adrenergically-mediated vasoconstriction. Therefore, ATP may be responsible for attenuating cutaneous vasoconstriction upon engagement of the cutaneous active vasodilator system. The effect of ATP on cutaneous vasoconstriction remains unknown, however. PURPOSE: To test the hypothesis that ATP inhibits adrenergically-mediated cutaneous vasoconstriction. METHODS: 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 flux was measured by laser-Doppler flowmetry and was used to calculate cutaneous vascular conductance (CVC; skin blood flux/mean arterial pressure), which was later normalized to peak CVC achieved with sodium nitroprusside infusion combined with local skin heating to ∼42 °C. Two microdialysis probes were perfused with 30 mM ATP while the other 2 were flow matched via administration of 2.8 mM adenosine to serve as control sites. After achieving stable baselines, adrenergically-mediated cutaneous vasoconstriction was induced by administration of 1·10-4 M tyramine at all sites while ATP and adenosine continued to be infused at their respective sites. RESULTS: Administration of tyramine decreased CVC ∼34% at all sites (P<0.001), but the magnitude of decrease was not different between sites (P=0.32 for interaction). CONCLUSIONS: These findings indicate that unlike in skeletal muscle, ATP does not attenuate adrenergically-mediated vasoconstriction in human skin. Supported by NIH Grants HL61388 & HL84072.