Vasomotor activity of diadenosine triphosphate and diadenosine tetraphosphate in isolated arteries

Dinucleotides diadenosine triphosphate (AP3A) and diadenosine tetraphosphate (AP4A) are released from platelet-dense granules upon agonist-induced platelet aggregation. Since most platelet-derived compounds simultaneously affect aggregation and vascular tone, we investigated whether AP3A and AP4A have vasoactive properties. Experiments were performed in isolated, saline-perfused segments of rabbit mesenteric arteries precontracted with norepinephrine. In segments with intact endothelium, both dinucleotides (1-10 microM) induced vasodilation, with AP3A responses significantly greater. Vasodilator responses to AP3A in endothelium-denuded segments were not significantly different from those in segments with intact endothelium but those to AP4A in endothelium-intact segments were reversed to a pronounced contraction after endothelium removal. Likewise, pretreatment of endothelium-intact segments with gossypol (3 microM) reversed dilator responses to acetylcholine and to AP4A into contractions, whereas AP3A-induced dilation was not affected. In segments with intact endothelium but pretreated with reactive blue (10 microM), AP4A also induced a contraction. Dilator response to AP3A was not affected. High-performance liquid chromatographic analysis of effluent from vascular segments showed that neither AP3A nor AP4A was degraded during passage through segments. These results indicate that in rabbit mesenteric arteries both nucleotides act directly, and not through their hydrolysis products, on endothelial (AP4A) and/or smooth muscle receptors. The endothelium-dependent dilator effect of AP4A, is probably mediated by endothelial P2y-purinoceptors.