Abstract
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.
Footnotes
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Send reprint requests to: Dr. M. Steinmetz, Medizinische Poliklinik, Universität Münster, Albert-Schweitzer Strasse 33, 48129 Münster, Germany. E-mail:steinme{at}uni-muenster.de
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↵1 This study was supported by a grant of the Center for Interdisciplinary Clinical Research (IZKF, project A1) at the Medical Faculty of the University of Münster (BMBF 01 KS 9604/0) and the Cardiovascular Research Institute Maastrich at the University of Maastricht.
- Abbreviations:
- APnA
- diadenosine polyphosphates
- MrA
- mesenteric resistance artery
- SEA
- superior epigastric artery
- 6-OHDA
- 6-hydroxydopamine
- α,β-me ATP
- α,β-methylene ATP
- PPADS
- pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonic acid
- KRB
- Krebs-Ringer-bicarbonate solution
- Received February 14, 2000.
- Accepted May 4, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
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