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1 Pharmacology-Toxicology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
2 Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
3 Pharmacology-Toxicology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
* To whom correspondence should be addressed. E-mail: N.Riksen{at}aig.umcn.nl.
The pressor response to exercise is of great importance in both physiology and pathophysiology. Whether endogenous adenosine is a trigger for this reflex remains controversial. Muscle interstitial adenosine concentration can be determined by microdialysis. However, there are indications that local muscle cell damage by the microdialysis probe confounds these measurements in exercising muscle. Therefore we used the nucleoside uptake-inhibitor dipyridamole as pharmacological tool to bypass this confounding. We used microdialysis probes to measure endogenous adenosine in forearm skeletal muscle of healthy volunteers during 2 cycles of 15 minutes of intermittent isometric handgripping. During the second contraction dipyridamole (12 µg/min/dl forearm) was administered into the brachial artery. Dipyridamole potentiated the exercise-induced increase in dialysate adenosine from 0.30 ± 0.08 to 0.48 ± 0.10 µmol/l (n=9, P<0.05), but did not potentiate the exercise-induced increase in blood pressure. A time-control study without dipyridamole revealed no difference in exercise-induced increase in adenosine between both contractions (n=8). To exclude that the dipyridamole-induced increase in dialysate adenosine originates from extravasation of increased circulating adenosine, we simultaneously measured adenosine with microdialysis probes in forearm muscle and antecubital vein. In a separate group of 9 volunteers, simultaneous intrabrachial infusion of 100 µg/min/dl dipyridamole and 5 µg/min/dl adenosine increased dialysate adenosine from the intravenous but not the interstitial probe, indicating preserved endothelial barrier function for adenosine. We conclude that dipyridamole significantly inhibits uptake of interstitial adenosine without affecting the pressor response to exercise, suggesting that interstitial adenosine is not involved in the pressor response to rhythmic isometric exercise.
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