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Mitochondrial monoamine oxidase‐A‐mediated hydrogen peroxide generation enhances 5‐hydroxytryptamine‐induced contraction of rat basilar artery
Author(s) -
Poon Christina Chui Wa,
Seto Sai Wang,
Au Alice Lai Shan,
Zhang Qian,
Li Rachel Wai Sum,
Lee Wayne Yuk Wai,
Leung George Pak Heng,
Kong Siu Kai,
Yeung John Hok Keung,
Ngai Sai Ming,
Ho Ho Pui,
Lee Simon Ming Yuen,
Chan Shun Wan,
Kwan Yiu Wa
Publication year - 2010
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2010.00941.x
Subject(s) - clorgyline , medicine , basilar artery , chemistry , monoamine oxidase , endocrinology , contraction (grammar) , biochemistry , enzyme
BACKGROUND AND PURPOSE We evaluated the role(s) of monoamine oxidase (MAO)‐mediated H 2 O 2 generation on 5‐hydroxytryptamine (5‐HT)‐induced tension development of isolated basilar artery of spontaneously hypertensive rats (SHR) and normotensive Wistar‐Kyoto (WKY) rats. EXPERIMENTAL APPROACH 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. KEY RESULTS 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 H 2 O 2 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 H 2 O 2 in SHR compared with WKY. Whole‐cell iberiotoxin‐sensitive Ca 2+ ‐activated K + (BK Ca ) amplitude measured in myocytes of SHR was approximately threefold greater than that in WKY (at +60 mV: 7.61 ± 0.89 pA·pF −1 vs. 2.61 ± 0.66 pA·pF −1 ). In SHR myocytes, 5‐HT caused a greater inhibition (clorgyline‐, polyethylene glycol‐catalase‐ and reduced glutathione‐sensitive) of BK Ca amplitude than in those from WKY. CONCLUSIONS AND IMPLICATIONS 5‐HT caused an increased generation of mitochondrial H 2 O 2 via MAO‐A‐mediated 5‐HT metabolism, which caused a greater inhibition of BK Ca gating in basilar artery myocytes, leading to exaggerated basilar artery tension development in SHR.