TY - JOUR T1 - Diadenosine Polyphosphates Cause Contraction and Relaxation in Isolated Rat Resistance Arteries JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1175 LP - 1181 VL - 294 IS - 3 AU - Martin Steinmetz AU - Eberhard Schlatter AU - Harry Alexander Jozef Struijker Boudier AU - Karl Heinz Rahn AU - Jozef Gabriel Rita De Mey Y1 - 2000/09/01 UR - http://jpet.aspetjournals.org/content/294/3/1175.abstract N2 - The effects of diadenosine polyphosphates (APnA; n= 3–6) and adenine nucleotides on contractile reactivity of isolated rat mesenteric resistance arteries (MrA) and superior epigastric arteries (SEA), which display a dense and 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: α,β-methylene ATP (α,β-meATP) > AP5A > AP6A > AP4A > ATP > ADP > AP3A. Contractions were stable during several minutes in SEA but highly transient in MrA. They were reduced after exposure to 10 μM α,β-meATP and by 10 μM of the P2X antagonist pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonic acid. During phenylephrine (10 μM)-induced contractions, the agonists induced a further contraction in SEA. In MrA, however, further contraction was followed by marked relaxation. The rank order of relaxing potency was comparable to that of the contractile potency of agonists. Also, the relaxing effects of APnA were blunted by 10 μM pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonic acid and after exposure to α,β-meATP. In vitro and in vivo sympathectomy with 6-hydroxydopamine and removal of the endothelium did not modify the effects of APnA in MrA. Thus, the contractile effects of APnA in resistance arteries 1) are due to a P2X purinoceptor-mediated stimulation of the smooth muscle; 2) depend on the length of the phosphate chain; and 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 regional heterogeneity of APnA effects cannot be attributed to a direct neurogenic influence. The American Society for Pharmacology and Experimental Therapeutics ER -