Diadenosine pentaphosphate vasodilates the forearm vascular bed: inhibition by theophylline and augmentation by dipyridamole.
BACKGROUND
In rats, diadenosine pentaphosphate (AP(5)A) has been implicated in the pathogenesis of essential hypertension. This study describes for the first time the vasomotor action of AP(5)A in humans by means of the "perfused forearm technique."


RESULTS
AP(5)A evoked a dose-dependent forearm vasodilator response equal to that of adenosine but less than that of adenosine triphosphate (ATP) at equimolar doses. The P(1)-purinoceptor antagonist theophylline (0.28 micromol/min per deciliter) reduced the percentage decrease in forearm vascular resistance (FVR) to AP(5)A (0.6, 6, and 20 nmol/min/dL): -8% +/- 6%, -50% +/- 6%, and -68% +/- 4% during saline solution versus -7% +/- 4%, -33% +/- 5%, and -45% +/- 6% during theophylline (mean +/- standard error [SE]; ANOVA for repeated measures; P <.05 for the interaction between purine dose and theophylline; n = 10). An inhibitor of equilibrative nucleoside transport, dipyridamole (7.4 nmol/min per deciliter), augmented the AP(5)A (0.6 and 6 nmol/min per deciliter)-induced reduction in FVR as follows: -34% +/- 6% and -67% +/- 5% during saline versus -49% +/- 5% and -80% +/- 3% during dipyridamole (P <.05 for the effect of dipyridamole; n = 6). The bivalent cation chelator ethylenediaminetetra-acetic acid (EDTA) inhibited the rapid degradation of AP(5)A in vitro. In vivo, the highest tolerated intra-arterial EDTA dose was not sufficient to inhibit AP(5)A metabolism.


CONCLUSIONS
Intra-arterial AP(5)A caused a dose-dependent reduction in FVR. This is, at least in part, mediated by its degradation product adenosine. The data do not support an in vivo vasoconstrictor action of AP(5)A, and as such AP(5)A does not seem likely to contribute to the pathogenesis of primary hypertension in humans.
van Ginneken
Egidia E M
EE
Department of General Internal Medicine, University Medical Center Nijmegen, The Netherlands.
Rongen
Gerard A
GA
Russel
Frans G m
FG
Smits
Paul
P
D000328:Adult; D016049:Didanosine / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology*; D004176:Dipyridamole / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004492:Edetic Acid / Q000494:pharmacology; D005260:Female; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D008297:Male; D012016:Reference Values; D013806:Theophylline / Q000008:administration & dosage / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*
D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D004176:Dipyridamole; D004492:Edetic Acid; D013806:Theophylline; D016049:Didanosine