Mitochondrial monoamine oxidase-A-mediated hydrogen peroxide generation enhances 5-hydroxytryptamine-induced contraction of rat basilar artery

British Journal of Pharmacology
Christina Chui Wa PoonYiu Wa Kwan

Abstract

We evaluated the role(s) of monoamine oxidase (MAO)-mediated H₂O₂ generation on 5-hydroxytryptamine (5-HT)-induced tension development of isolated basilar artery of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Basilar artery (endothelium-denuded) was isolated for tension measurement and Western blots. Enzymically dissociated single myocytes from basilar arteries were used for patch-clamp electrophysiological and confocal microscopic studies. Under resting tension, 5-HT elicited a concentration-dependent tension development with a greater sensitivity (with unchanged maximum tension development) in SHR compared with WKY (EC(50) : 28.4 ± 4.1 nM vs. 98.2 ± 9.4 nM). The exaggerated component of 5-HT-induced tension development in SHR was eradicated by polyethylene glycol-catalase, clorgyline and citalopram whereas exogenously applied H₂O₂ enhanced the 5-HT-elicited tension development in WKY. A greater protein expression of MAO-A was detected in basilar arteries from SHR than in those from WKY. In single myocytes and the entire basilar artery, 5-HT generated (clorgyline-sensitive) a greater amount of H₂O₂ in SHR compared with WKY. Whole-cell iberiotoxin-sensitive Ca(2+) -activated K(+) (BK(Ca) ) am...Continue Reading

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Jul 19, 2014·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Takayuki MatsumotoTsuneo Kobayashi
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Related Concepts

Iberiotoxin
Structure of Basilar Artery
Dose-Response Relationship, Drug
Oxydol
Hypertensive Disease
Mitochondria
Monoamine Oxidase
Polypeptides
Rats, Inbred SHR
Rats, Inbred WKY

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