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

Noradrenaline is responsible for eliciting approximate to 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 degrees C). In protocol 1, the following solutions were infused: (i) lactated Ringer solution (control); (ii) 10mm l-NAME; and (iii) purinergic receptor blockade with 1mm 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 5mm yohimbine plus 1mm 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 (%CVCBASELINE). l-NAME was used to block the vasodilatory influence of ATP and unmask the P2X-mediated VC response to exogenous ATP infusion (-21 +/- 6%CVCBASELINE). During cooling, the VC response (control, -39 +/- 8%CVCBASELINE) was attenuated at the suramin site (-21 +/- 4%CVCBASELINE) and further blunted with combined adrenoreceptor blockade (-9 +/- 3%CVCBASELINE; P<0.05). Compared with the control site (-22 +/- 5%CVCBASELINE), suramin inhibited pharmacologically induced VC to tyramine (-12 +/- 6%CVCBASELINE; P<0.05), which displaces adrenergic neurotransmitters from axon terminals. These data indicate that ATP contributes to the cutaneous VC response in humans.