title: No direct role for A1/A2 adenosine receptor activation to reflex cutaneous vasodilatation during whole-body heat stress in humans.
abstract: OBJECTIVE
  The precise mechanisms underlying reflex cutaneous vasodilatation during hyperthermia remain unresolved. The purpose of this study was to investigate a potential contribution of adenosine A1/A2 receptor activation to reflex cutaneous vasodilatation.
  
  
  METHODS
  Eight subjects were equipped with four microdialysis fibres on the left forearm, and each fibre was randomly assigned one of four treatments: (1) lactated Ringer's (control); (2) 4 mm of the non-selective A1/A2 adenosine receptor antagonist theophylline; (3) 10 mm L-NAME to inhibit nitric oxide (NO) synthase; and (4) combined 4 mm theophylline and 10 mm L-NAME. Laser-Doppler flowmetry (LDF) was used as an index of skin blood flow, and blood pressure was measured beat-by-beat via photoplethysmography and verified via brachial auscultation. Whole-body heat stress to raise oral temperature 0.8 °C above baseline was induced via water-perused suits. Cutaneous vascular conductance (CVC) was calculated as LDF/mean arterial pressure and normalized to maximal (%CVC max) via infusion of 28 mm nitroprusside and local heating to 43 °C.
  
  
  RESULTS
  There was no difference between control (65 ± 5%CVC max) and theophylline (63 ± 5%CVC max) sites. L-NAME (44 ± 4%CVC max) and theophylline + L-NAME (32 ± 3%CVC max) sites were significantly attenuated compared to both control and theophylline only sites (P<0.05), and combined theophylline + L-NAME sites were significantly reduced compared to L-NAME only sites (P<0.05).
  
  
  CONCLUSIONS
  These data suggest A1/A2 adenosine receptor activation does not directly contribute to cutaneous active vasodilatation; however, a role for A1/A2 adenosine receptor activation is unmasked when NO synthase is inhibited.
authors.affiliation: Department of Kinesiology, Kansas State University, Manhattan, KS 66506, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Fieger
authors.forename: B J
authors.initials: BJ
authors.lastname: Wong
mesh_terms: D000328:Adult; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D018869:Heat-Shock Response / Q000502:physiology*; D006801:Humans; D008297:Male; D017551:Microdialysis; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000187:drug effects; D009599:Nitroprusside / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists / Q000494:pharmacology; D043682:Receptor, Adenosine A1 / Q000187:drug effects / Q000502:physiology*; D043683:Receptors, Adenosine A2 / Q000187:drug effects / Q000502:physiology*; D012867:Skin / Q000098:blood supply*; D013806:Theophylline / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D058915:Purinergic P1 Receptor Antagonists; D043682:Receptor, Adenosine A1; D043683:Receptors, Adenosine A2; D014665:Vasodilator Agents; D009599:Nitroprusside; D013806:Theophylline; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester