title: Dipyridamole enhances ischaemia-induced reactive hyperaemia by increased adenosine receptor stimulation.
abstract: OBJECTIVE
  Dipyridamole enhances post-occlusive reactive hyperaemia (PORH) in the human forearm vascular bed. We hypothesize that this effect is completely mediated by increased adenosine receptor stimulation. To test this hypothesis, the effect of caffeine (an adenosine receptor antagonist) on dipyridamole-induced augmentation of PORH was explored.
  
  
  METHODS
  The forearm vasodilator responses to three increasing periods of forearm ischaemia (2, 5 and 13 min) were determined during placebo infusion. Forty minutes after the last reperfusion period, this procedure was repeated during intra-arterial infusion of dipyridamole (7.4 nmol min(-1) per 100 ml forearm). At least 2 weeks later, this whole procedure was repeated, but now in the presence of caffeine (90 microg min(-1) per 100 ml volume).
  
  
  RESULTS
  After 2, 5 and 13 min of ischaemia, the average forearm blood flow increased to 5.6+/-0.7, 9.7+/-1.3 and 34.5+/-2.1 ml min(-1) per 100 ml. After infusion of dipyridamole into the brachial artery, these numbers were significantly increased to 7.7+/-0.8, 12.5+/-1.5 and 41.6+/-3.1 ml min(-1) per 100 ml. This response was abolished by the concomitant infusion of caffeine (6.6+/-0.5, 10.2+/-0.6, 35.1+/-2.2 (caffeine) versus 7.4+/-0.4, 10.5+/-0.6, 33.7+/-2.2 ml min(-1)per 100 ml (caffeine/dipyridamole)).
  
  
  CONCLUSIONS
  Caffeine prevented the augmenting effect of dipyridamole on PORH. This indicates that dipyridamole-induced augmentation of PORH is mediated via increased adenosine receptor stimulation as a result of elevated extracellular formation of adenosine during ischaemia.
authors.affiliation: Department of Pharmacology and Toxicology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. p.meijer@anes.umcn.nl
authors.forename: P
authors.initials: P
authors.lastname: Meijer
authors.forename: C W
authors.initials: CW
authors.lastname: Wouters
authors.forename: P H H
authors.initials: PH
authors.lastname: van den Broek
authors.forename: G J
authors.initials: GJ
authors.lastname: Scheffer
authors.forename: N P
authors.initials: NP
authors.lastname: Riksen
authors.forename: P
authors.initials: P
authors.lastname: Smits
authors.forename: G A
authors.initials: GA
authors.lastname: Rongen
mesh_terms: D000328:Adult; D002110:Caffeine / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004176:Dipyridamole / Q000494:pharmacology*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D006940:Hyperemia / Q000209:etiology / Q000378:metabolism*; D007511:Ischemia / Q000503:physiopathology; D008297:Male; D043682:Receptor, Adenosine A1 / Q000187:drug effects* / Q000378:metabolism; D043683:Receptors, Adenosine A2 / Q000187:drug effects* / Q000378:metabolism; D012039:Regional Blood Flow / Q000187:drug effects; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D000697:Central Nervous System Stimulants; D043682:Receptor, Adenosine A1; D043683:Receptors, Adenosine A2; D014665:Vasodilator Agents; D002110:Caffeine; D004176:Dipyridamole