Evidence for a functional vasoconstrictor role for ATP in the human cutaneous microvasculature

What is the central question of this study? In young adults, about half of the cold-related reduction in skin blood flow during cold exposure is mediated by noradrenaline, while the remainder is attributable to other substances co-released with noradrenaline that have yet to be identified. What is the main finding and its importance? Purinergic receptor blockade blunted the vasoconstriction response to whole-body cooling and to intradermal administration of tyramine. These results indicate that ATP is necessary to vasoconstrict blood vessels in the skin adequately and prevent heat loss in a cold environment. Noradrenaline is responsible for eliciting ∼60% of the reflex cutaneous vasoconstriction (VC) response in young adults, while the remainder is attributable to one or more unidentified co-released sympathetic adrenergic neurotransmitter(s). Inconsistent evidence has placed neuropeptide Y in this role; however, other putative cotransmitters have yet to be tested. We hypothesize that ATP contributes to the reflex cutaneous VC response. Two protocols were conducted in young adults (n = 10); both involved the placement of three microdialysis probes in forearm skin and whole-body cooling (skin temperature = 30.5°C). In protocol 1, the following solutions were infused: (i) lactated Ringer solution (control); (ii) 10 mm l-NAME; and (iii) purinergic receptor blockade with 1 mm suramin plus l-NAME. In protocol 2, the following solutions were infused: (i) lactated Ringer solution; (ii) suramin plus l-NAME; and (iii) suramin plus l-NAME plus adrenoreceptor blockade with 5 mm yohimbine plus 1 mm propranolol. Laser Doppler flux (LDF) was measured over each microdialysis site, and cutaneous vascular conductance (CVC) was calculated (CVC = LDF/MAP) and expressed as percentage changes from baseline (%ΔCVC_BASELINE ). l-NAME was used to block the vasodilatory influence of ATP and unmask the P₂ X-mediated VC response to exogenous ATP infusion (-21 ± 6%ΔCVC_BASELINE ). During cooling, the VC response (control, -39 ± 8%ΔCVC_BASELINE ) was attenuated at the suramin site (-21 ± 4%ΔCVC_BASELINE ) and further blunted with combined adrenoreceptor blockade (-9 ± 3%ΔCVC_BASELINE ; P < 0.05). Compared with the control site (-22 ± 5%ΔCVC_BASELINE ), suramin inhibited pharmacologically induced VC to tyramine (-12 ± 6%ΔCVC_BASELINE ; P < 0.05), which displaces adrenergic neurotransmitters from axon terminals. These data indicate that ATP contributes to the cutaneous VC response in humans.