title: Extracellular adenosine initiates rapid arteriolar vasodilation induced by a single skeletal muscle contraction in hamster cremaster muscle.
abstract: OBJECTIVE
  Recent studies suggest that adenosine (ADO) can be produced extracellularly in response to skeletal muscle contraction. We tested the hypothesis that a single muscle contraction produces extracellular ADO rapidly enough and in physiologically relevant concentrations to be able to contribute to the rapid vasodilation that occurs at the onset of muscle contraction.
  
  
  METHODS
  We stimulated four to five skeletal muscle fibres in the anaesthetized hamster cremaster preparation in situ and measured the change in diameter of arterioles at a site of overlap with the stimulated muscle fibres before and after a single contraction (stimulus frequencies: 4, 20 and 60 Hz; 250 ms train duration). Muscle fibres were stimulated in the absence and presence of non-specific ADO membrane receptor antagonists 8-phenyltheophylline (8-PT, 10(-6) M) or xanthine amine congener (XAC, 10(-6) M) or an inhibitor of an extracellular source of ADO, ecto-5'-nucleotidase inhibitor α,β-methylene adenosine 5'-diphosphate (AMPCP, 10(-5) M).
  
  
  RESULTS
  We observed that the dilatory event at 4 s following a single contraction was significantly inhibited at all stimulus frequencies by an average of 63.9 ± 2.6% by 8-PT. The 20-s dilatory event that occurred at 20 and 60 Hz was significantly inhibited by 53.6 ± 2.6 and 73.8 ± 2.3% by 8-PT and XAC respectively. Further, both the 4- and 20-s dilatory events were significantly inhibited by AMPCP by 78.6 ± 6.6 and 67.1 ± 1.5%, respectively, at each stimulus frequency tested.
  
  
  CONCLUSIONS
  Our data show that ADO is produced extracellularly during a single muscle contraction and that it is produced rapidly enough and in physiologically relevant concentrations to contribute to the rapid vasodilation in response to muscle contraction.
authors.affiliation: Department of Human Biology and Nutritional Science, University of Guelph, Guelph, ON, Canada.
authors.forename: G A
authors.initials: GA
authors.lastname: Ross
authors.forename: M L
authors.initials: ML
authors.lastname: Mihok
authors.forename: C L
authors.initials: CL
authors.lastname: Murrant
mesh_terms: D015720:5'-Nucleotidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D001160:Arterioles / Q000378:metabolism; D006224:Cricetinae; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D008647:Mesocricetus; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D058915:Purinergic P1 Receptor Antagonists / Q000494:pharmacology; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D058915:Purinergic P1 Receptor Antagonists; D015720:5'-Nucleotidase; D000241:Adenosine