Characterization of the Inhibitory Effect of Vascular Endothelium on Agonist-Induced Vasoconstriction in Rat Mesenteric Resistance Arteries
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概要
- 論文の詳細を見る
Vascular endothelium regulates vascular tone by releasing endothelium-derived vasoactive substances. We performed this study to characterize the inhibitory effect of the endothelium on vasoconstrictor stimuli in rat mesenteric vascular beds. Changes in perfusion pressure induced by continuous perfusion of Krebs solution containing methoxamine (α1-adrenoceptor agonist) or high KCl were measured over 180 min. In preparations with intact endothelium, methoxamine-induced vasoconstriction was time-dependently decreased to cause 60% – 80% reduction of the initial vasoconstriction level, while no reduction was observed in high-KCl–induced vasoconstriction. Endothelium removal significantly blunted the time-dependent reduction of methoxamine-induced vasoconstriction without affecting high-KCl–induced vasoconstriction. Neither a nitric oxide synthase inhibitor (<sc>L</sc>-NAME) nor indomethacin (cyclooxygenase inhibitor) altered the time-dependent reduction of vasoconstriction. High KCl, K+-channel inhibitors tetraethylammonium and apamin plus charybdotoxin, and 18α-glycyrrhetinic acid (18α-GA, a gap-junction inhibitor) significantly inhibited the time-dependent reduction of methoxamine-induced vasoconstriction. In preconstricted preparations, bolus injection of acetylcholine and Ca2+-ionophore A23187 (A23187) evoked a sharp vasodilation, which was inhibited by endothelium removal, high KCl and tetraethylammonium, but not indomethacin, <sc>L</sc>-NAME, or 18α-GA. However, 18α-GA plus <sc>L</sc>-NAME inhibited vasodilation induced by A23187, but not acetylcholine. These findings suggest that endothelium-derived hyperpolarizing factor (EDHF) via gap junctions mainly counteracts vasoconstriction induced by methoxamine in mesenteric resistance arteries.
- 社団法人 日本薬理学会の論文
- 2008-09-20
著者
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Jin Xin
Department Of Clinical And Pharmaceutical Science Graduate School Of Medicine Dentistry And Pharmace
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Jin Xin
Department Of Applied Chemistry Harbin Institute Of Technology
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Zamami Yoshito
Department Of Clinical And Pharmaceutical Science Graduate School Of Medicine Dentistry And Pharmace
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Kawasaki Hiromu
Dep. Of Clinical Pharmacology Graduate School Of Medicine Dentistry And Pharmaceutical Sciences Okay
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Kawasaki Hiromu
Department Of Clinical Pharmaceutical Science Graduate School Of Medicine Dentistry And Pharmaceutic
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Koyama Toshihiro
Dep. Of Pharmaceutical Care And Health Sciences Graduate School Of Medicine Dentistry And Pharmaceut
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Koyama Toshihiro
Department Of Applied Chemistry Faculty Of Engineering Hiroshima University
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Kitamura Yoshihisa
Department Of Neurobiology Kyoto Pharmaceutical University
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Kitamura Yoshihisa
Department Of Pharmaceutical Care And Health Science Graduate School Of Medicine Dentistry And Pharm
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Kawasaki Hiromu
岡山大学 医歯薬学総合研究科臨床薬学
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Kawasaki Hiromu
Department Of Clinical And Pharmaceutical Science Graduate School Of Medicine Dentistry And Pharmace
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Kawasaki Yoichi
Department Of Pharmacy Okayama University Hospital
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SATOH OTONASHI
Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceut
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SUN Pengyuan
Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceut
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Satoh-Otonashi Yukiko
Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceut
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Satoh Otonashi
Department Of Clinical Pharmaceutical Science Graduate School Of Medicine Dentistry And Pharmaceutic
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Kitamura Yoshihisa
Department Of Pharmaceutical Care And Health Science Graduate School Of Medicine Dentistry And Pharm
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SUN Pengyuan
Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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Kitamura Yoshihisa
Department of Clinical Pharmacy, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Japan
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KITAMURA Yoshihisa
Department of Clinical Pharmacy, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
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