title: Evidence for a functional vasoconstrictor role for ATP in the human cutaneous microvasculature.
abstract: 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 (%ΔCVCBASELINE). l-NAME was used to block the vasodilatory influence of ATP and unmask the P2X-mediated VC response to exogenous ATP infusion (-21 ± 6%ΔCVCBASELINE). During cooling, the VC response (control, -39 ± 8%ΔCVCBASELINE) was attenuated at the suramin site (-21 ± 4%ΔCVCBASELINE) and further blunted with combined adrenoreceptor blockade (-9 ± 3%ΔCVCBASELINE; P < 0.05). Compared with the control site (-22 ± 5%ΔCVCBASELINE), suramin inhibited pharmacologically induced VC to tyramine (-12 ± 6%ΔCVCBASELINE; P < 0.05), which displaces adrenergic neurotransmitters from axon terminals. These data indicate that ATP contributes to the cutaneous VC response in humans.
authors.affiliation: Department of Physical Therapy, Des Moines University, Des Moines, IA, USA.
authors.forename: James A
authors.identifier: 0000-0002-5179-1434
authors.initials: JA
authors.lastname: Lang
authors.affiliation: Department of Physical Therapy, Des Moines University, Des Moines, IA, USA.
authors.forename: Alex C
authors.initials: AC
authors.lastname: Krajek
authors.affiliation: Department of Neuroscience, Drake University, Des Moines, IA, USA.
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Smaller
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000328:Adult; D001833:Body Temperature Regulation / Q000187:drug effects; D003080:Cold Temperature; D005260:Female; D005542:Forearm / Q000098:blood supply / Q000502:physiology; D006801:Humans; D008297:Male; D055806:Microvessels / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D009638:Norepinephrine / Q000378:metabolism; D011433:Propranolol / Q000008:administration & dosage; D012018:Reflex / Q000502:physiology; D012039:Regional Blood Flow / Q000502:physiology; D012867:Skin / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D012881:Skin Temperature / Q000187:drug effects / Q000502:physiology; D013498:Suramin / Q000008:administration & dosage; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000378:metabolism*; D015016:Yohimbine / Q000008:administration & dosage
chemical_list: D014662:Vasoconstrictor Agents; D015016:Yohimbine; D013498:Suramin; D000255:Adenosine Triphosphate; D011433:Propranolol; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine
keywords: P2-purinergic receptor; cotransmitter; microdialysis; skin blood flow; thermoregulation