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Clin Pharmacol Ther. 2002 Jun;71(6):448-56.

Diadenosine pentaphosphate vasodilates the forearm vascular bed: inhibition by theophylline and augmentation by dipyridamole.

Author information

1
Department of General Internal Medicine, University Medical Center Nijmegen, The Netherlands.

Abstract

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.

CONCLUSION:

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.

PMID:
12087348
DOI:
10.1067/mcp.2002.124469
[Indexed for MEDLINE]

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