Mechanisms Underlying Pioglitazone-Mediated Relaxation in Isolated Blood Vessel
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概要
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Pioglitazone is a widely used anti-type 2 diabetic drug. Beside its insulin-sensitizing effects, pioglitazone exerts preventive roles against ischemic heart disease. Since one possible explanation is anti-hypertensive action, we examined effects of pioglitazone on contractility of isolated blood vessel. Endothelium-intact [End (+)] or -removed [End (−)] rat aorta is isolated and isometric tension is recorded. In both End (+) and End (−) aorta, pretreatment with pioglitazone (3 – 10 μM, 30 min) inhibited noradrenaline (NA) (1 nM – 1 μM)-induced contraction. In NA (100 nM)-precontracted aorta, pioglitazone (1 – 10 μM) directly induced a relaxation. The relaxant effect is higher in End (−) aorta than in End (+) aorta. In End (+) aorta, NG-nitro-<sc>L</sc>-arginine methyl ester (100 μM) significantly inhibited the relaxation. In End (−) aorta, neither indomethacin nor cimetidine affected the relaxation, but tetraethylammonium (10 mM) inhibited it. Furthermore, the relaxation was significantly inhibited by a voltage-dependent K+ (KV)-channel blocker, 4-aminopyridine (1 mM), or an inward rectifying K+ (KIR)-channel blocker, BaCl2 (1 mM). GW9662 (2 μM), a blocker of peroxisome proliferator-activated receptor (PPAR)-γ was ineffective against the relaxation. The present study demonstrated that pioglitazone causes PPAR-γ–independent relaxation. While endothelium-dependent relaxation is mediated via nitric oxide, the endothelium-independent one is responsible for smooth muscle K+ (KV, KIR)-channel opening.
- 社団法人 日本薬理学会の論文
- 2008-11-20
著者
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Yamawaki Hideyuki
東京大学 農生命科研究
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Yamawaki Hideyuki
Department Of Veterinary Pharmacology Graduate School Of Agriculture And Life Sciences The Universit
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Yamawaki Hideyuki
Department Of Veterinary Pharmacology School Of Veterinary Medicine Kitasato University
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Yamawaki Hideyuki
Department Of Epidemiology Research Institute National Cardiovascular Center
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Hara Yukio
Department Of Veterinary Pharmacology School Of Veterinary Medicine And Animal Sciences Kitasato Uni
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Okada Muneyoshi
Department Of Veterinary Pharmacology Graduate School Of Agriculture And Life Sciences The Universit
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Okada Muneyoshi
Department Of Veterinary Pharmacology School Of Veterinary Medicine And Animal Sciences Kitasato Uni
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NOMURA Hidemi
Department of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University
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MUKOHDA Masashi
Department of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University
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Nomura Hidemi
Laboratory Of Veterinary Pharmacology School Of Veterinary Medicine Kitasato University
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Hara Yukio
Laboratory Of Veterinary Pharmacology School Of Veterinary Medicine Kitasato University
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Mukohda Masashi
Laboratory Of Veterinary Pharmacology School Of Veterinary Medicine Kitasato University
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