Low 4-aminopyridine concentration-induced contraction is mediated by neuronal noradrenaline in canine saphenous vein.
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 radio-labelled 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 microM) enhanced the basal tone of venous rings without and with endothelium (maximum tone at 5 microM 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 microM 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 microM 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.
Kun
Attila
A
Division of Cardiovascular Pharmacology, Hungarian Academy of Sciences, Szeged, Hungary. kuna@phcol.szote.u-szeged.hu
Pataricza
János
J
Krassói
Irén
I
Szécsi
Mihály
M
Hohn
József
J
Varró
András
A
Papp
Julius Gy
JG
D015761:4-Aminopyridine / Q000008:administration & dosage*; D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism / Q000502:physiology*; D012501:Saphenous Vein / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D015761:4-Aminopyridine; D009638:Norepinephrine