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Mitochondrial monoamine oxidase-A-mediated hydrogen peroxide generation enhances 5-hydroxytryptamine-induced contraction of rat basilar artery.
- Source :
- British Journal of Pharmacology; Nov2010, Vol. 161 Issue 5, p1086-1098, 13p
- Publication Year :
- 2010
-
Abstract
- <bold>Background and Purpose: </bold>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.<bold>Experimental Approach: </bold>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.<bold>Key Results: </bold>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) ) 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.<bold>Conclusions and Implications: </bold>5-HT caused an increased generation of mitochondrial H₂O₂ 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- MITOCHONDRIAL pathology
MONOAMINE oxidase
HYDROGEN peroxide
SEROTONIN
LABORATORY rats
BASILAR artery
ELECTROPHYSIOLOGY
CELL metabolism
POTASSIUM metabolism
ANIMAL experimentation
CELLS
COMPARATIVE studies
CYTOLOGICAL techniques
DOSE-effect relationship in pharmacology
HYPERTENSION
RESEARCH methodology
MEDICAL cooperation
MICROSCOPY
MITOCHONDRIA
OXIDOREDUCTASES
PEPTIDES
POTASSIUM
RATS
RESEARCH
WESTERN immunoblotting
EVALUATION research
VASOCONSTRICTION
CHEMICAL inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 00071188
- Volume :
- 161
- Issue :
- 5
- Database :
- Complementary Index
- Journal :
- British Journal of Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 65012983
- Full Text :
- https://doi.org/10.1111/j.1476-5381.2010.00941.x