Influence of purinoceptor antagonism on diadenosine pentaphosphate-inducedhypotension in anesthetized rats

Diadenosine polyphosphates (ApnA; n = 3-6) are potent vasoactive agents in isolated vessels. Information on effects of ApnA in vivo is still limited d espite the fact that these compounds are starting to be used in humans. Thi s study was designed to compare the effects of ApnA and their possible meta bolites on blood pressure in vivo and to functionally identify purinoceptor s involved in their action. All four ApnA and their degradation products in duced a sustained drop of mean arterial blood pressure during i.v. infusion , which was fully reversible. The rank order of potency was Ap4A greater th an or equal to Ap6A > Ap5A = Ap3A = ATP = ADP > AMP greater than or equal t o adenosine, suggesting that the hypotensive effect is predominantly evoked by the original dinucleotides and not by their degradation products. The h ypotensive effect of Ap5A was reduced by the P2X and P2Y(1) purinoceptor an tagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid, the A(1) pu rinoceptor antagonist 8-cyclopentyl-1,3-dipropylxanthine, and the A(2) puri noceptor antagonist 3,7-dimethyl-1-propargylxanthine, The hypertensive effe ct by the prototype P2X receptor agonist alpha beta-methylene ATP was inhib ited by pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid, too. Purinoc eptor antagonists reduced the maximal effects of the agonists indicating a noncompetitive inhibition. In summary, the reported vasocontractile effect of ApnA seems to be limited to isolated preparations under resting tone con ditions; however, the systemic cardiovascular effects of all four ApnA are hypotensive, also making them candidates for blood pressure reduction in hu mans. These effects are fast in onset and easily reversible. Activation of different purinoceptors in the vasculature (most probably P2Y(1) and A(2) r eceptors) contributes to the Ap5A-induced decrease of mean arterial blood p ressure.