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

New FindingsWhat 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 m m l ‐NAME; and (iii) purinergic receptor blockade with 1 m m 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 m m yohimbine plus 1 m m 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 P 2 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.