Dipyridamole enhances ischemia‐induced reactive hyperemia by increased adenosine receptor stimulation

Abstract

Introduction: Dipyridamole enhances post‐occlusive reactive hyperemia (PORH) in the human forearm. The mechanism of this potentiation remains to be elucidated. We hypothesize that dipyridamole augments PORH by increasing interstitial adenosine and subsequent stimulation of adenosine receptors. To test this hypothesis, the effect of caffeine (an adenosine A1 and A2 receptor antagonist) on dipyridamole‐induced augmentation of PORH was explored.Methods: Eight healthy volunteers (6 female; age 19–24 year) abstained from caffeine intake for at least 24 hours. The brachial artery was cannulated for drug infusion. After forearm circulation had been occluded for 5 minutes and starting immediately upon reperfusion, forearm blood flow was measured for 5 minutes using venous occlusion mercury‐in‐silastic strain gauge plethysmography. At least one hour after reperfusion, this procedure was repeated during intra‐arterial infusion of dipyridamole (7.4 nmol/min/dl forearm). At least two weeks later, this whole procedure was repeated, but now in the presence of caffeine (0.46 μmol/min/dl forearm).Statistics: For each subsequent minute, forearm blood flow was averaged to one value. An ANOVA for repeated measures was performed with caffeine, dipyridamole and reperfusion time as within‐subject factors. Results are expressed as mean ± SEM.Results: FBF: forearm blood flowP < 0.05 for the effect of dipyridamole on PORHP > 0.5 for the effect of caffeine on PORHP < 0.01 for the interaction between caffeine and dipyridamole.Conclusions: Caffeine abolishes the augmenting effect of dipyridamole on PORH. This indicates that adenosine receptors are involved in the dipyridamole‐induced augmentation of PORH.