Neurogenic Contraction Induced by the Antiarrhythmic Compound, AVE 0118, in Rat Small Mesenteric Arteries

The purpose of this study was to investigate the vasoactivity of two inhibitors of potassium ion (K+) channels, a potential antiarrhythmic compound, AVE 0118, and 4‐aminopyridine (4‐AP). Basal and stimulated tones of rat small mesenteric arteries as well as the possible involvement of KV1.5 ion chan...

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Published in:Basic & clinical pharmacology & toxicology 2014-10, Vol.115 (4), p.315-320
Main Authors: Kun, Attila, Seprényi, György, Varró, András, Papp, Julius Gy, Pataricza, János
Format: Article
Language:English
Subjects:
4-Aminopyridine - pharmacology
Animals
Anti-Arrhythmia Agents - pharmacology
Biological and medical sciences
Biphenyl Compounds - pharmacology
Electric Stimulation
Immunohistochemistry
Kv1.5 Potassium Channel - metabolism
Male
Medical sciences
Mesenteric Arteries - drug effects
Microscopy, Confocal
Muscle Contraction - drug effects
Norepinephrine - pharmacology
Pharmacology. Drug treatments
Potassium Channel Blockers - pharmacology
Rats
Rats, Sprague-Dawley
Receptors, Adrenergic, alpha-1 - metabolism
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Summary:The purpose of this study was to investigate the vasoactivity of two inhibitors of potassium ion (K+) channels, a potential antiarrhythmic compound, AVE 0118, and 4‐aminopyridine (4‐AP). Basal and stimulated tones of rat small mesenteric arteries as well as the possible involvement of KV1.5 ion channel in the mechanism of vascular effect induced by the compounds were analysed. The standard organ bath technique for vascular tone and immunohistochemistry for the localization of ion channels in the arterial tissue were performed. Third‐ or fourth‐order branch of arterial segments was mounted in myographs for recording the isometric tension. AVE 0118 (10−5 M) and 4‐AP (10−5 M) modulated neither the basal tone nor the contraction induced by noradrenaline but increased the contraction evoked by electrical field stimulation, sensitive to the block of alpha‐1 adrenergic receptors. KV1.5 ion channel‐specific immunostaining demonstrated the presence of immunoreactive nerves, and Schwann‐cell‐specific (S100) immunostaining confirmed the presence of myelin sheath in rat small mesenteric arteries. The study supports an indirect, sympathetic effect of AVE 0118 similar to that of 4‐AP, which is mediated, at least in part, by blocking neuronal KV1.5 type potassium ion channels in the medio‐adventitial layer of rat small mesenteric artery.
ISSN:1742-7835
1742-7843
DOI:10.1111/bcpt.12225