Diadenosine polyphosphates cause contraction and relaxation in isolated rat resistance arteries

The effects of diadenosine polyphosphates (APnA; n = 3-6) and adenine nucle otides on contractile reactivity of isolated rat mesenteric resistance arte ries (MrA) and superior epigastric arteries (SEA), which display a dense an d sparse autonomic innervation, respectively, were evaluated. All agonists examined, except adenosine and AMP, induced contractions. The rank order of potency was similar in both arteries: alpha,beta-methylene ATP (alpha,beta -meATP) > AP5A > AP6A > AP4A > ATP > ADP > APBA. Contractions were stable d uring several minutes in SEA but highly transient in MrA. They were reduced after exposure to 10 mu M alpha,beta-meATP and by 10 mu M of the P2X antag onist pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid. During phenyle phrine (10 mu M)-induced contractions, the agonists induced a further contr action in SEA. In MrA, however, further contraction was followed by marked relaxation. The rank order of relaxing potency was comparable to that of th e contractile potency of agonists. Also, the relaxing effects of APnA were blunted by 10 mu M pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid an d after exposure to alpha,beta-meATP. In vitro and in vivo sympathectomy wi th 6-hydroxydopamine and removal of the endothelium did not modify the effe cts of APnA in MrA. Thus, the contractile effects of APnA in resistance art eries 1) are due to a P2X purinoceptor-mediated stimulation of the smooth m uscle; 2) depend on the length of the phosphate chain; acid 3) are followed by endothelium-independent relaxing effects in MrA but not SEA, which may involve receptors that are similar to those mediating contraction. The regi onal heterogeneity of APnA effects cannot be attributed to a direct neuroge nic influence.