Low 4-aminopyridine concentration-induced contraction is mediated by neuronal noradrenaline in canine saphenous vein

Attila Kun, János Pataricza, Irén Krassói, Mihály Szécsi, József Hohn, András Varró, Julius Gy Papp

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Abstract

4-Aminopyridine (4-AP), a known inhibitor of the voltage-dependent potassium channels, is able to increase the basal tone of different types of blood vessel preparations. In order to determine the efficiency of 4-AP in veins and to clarify its possible mechanism of action, the aim of the present study was to determine the basal tone and release of radiolabelled tissue noradrenaline (NA) after administration of low 4-AP concentrations. Experiments were performed in canine saphenous vein in the absence and presence of functional endothelium. 4-AP (0.012-5 μM) enhanced the basal tone of venous rings without and with endothelium (maximum tone at 5 μM 4-AP: 2.20±1.29 and 1.3±0.57 mN, respectively). NA stores of the venous tissue were loaded by adding 1 mM NA to the tissue for 10 min and then washed out. After loading the NA-stores of venous tissue, 4-AP-induced contractions were significantly increased both in the absence and presence of endothelium (maximum tone at 5 μM 4-AP after loading with NA: 10.51±3.64 and 10.52±4.69 mN, respectively). Following NA loading, chemical denervation of the endothelium denuded venous preparations by 0.5 mM 6-hydroxydopamine (6-OHDA) completely abolished the contractions evoked by 4-AP. After incubation of the saphenous preparations with 3H-NA, 5 μM 4-AP significantly increased tritium-efflux from the tissue. These results provide evidence for the efficiency of 4-AP on the basal tone of isolated canine saphenous vein when applied in low concentrations. Furthermore, it is suggested that this action of 4-AP may considerably depend on the release of NA from the perivascular nerve endings.

Original languageEnglish
Pages (from-to)7-11
Number of pages5
JournalVascular Pharmacology
Volume39
Issue number1-2
DOIs
Publication statusPublished - Jul 1 2002

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Keywords

  • 4-Aminopyridine
  • Canine saphenous vein
  • Release of noradrenaline

ASJC Scopus subject areas

  • Physiology
  • Molecular Medicine
  • Pharmacology

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