Losartan Normalizes Endothelium-Derived Hyperpolarizing Factor–Mediated Relaxation by Activating Ca2+-Activated K+ Channels in Mesenteric Artery From Type 2 Diabetic GK Rat
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概要
- 論文の詳細を見る
Ca2+-activated K+ (KCa) channels are important for endothelium-derived hyperpolarizing factor (EDHF) signaling. Since treatment with angiotensin II receptor blockers (ARBs) improves vasculopathies in type 2 diabetic patients, we asked whether the EDHF-type relaxation and its associated KCa channels [small (SKCa)–, intermediate (IKCa)–, and large (BKCa)–conductance channels] are abnormal in mesenteric arteries isolated from Goto-Kakizaki (GK) rats at the chronic stage of type 2 diabetes (34 – 38 weeks) and whether an ARBs (losartan, 25 mg·kg−1·day−1 for 2 weeks) might correct these abnormalities. Although the acetylcholine chloride–induced EDHF-type relaxation in mesenteric arteries from GK rats was reduced versus the Wistar controls, it was significantly restored by losartan treatment. The SKCa-blocker apamin or the IKCa-blocker 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34) inhibited such relaxations in the losartan-treated or -untreated Wistar groups and in the losartan-treated GK group, but not in the losartan-untreated GK group. The BKCa-blocker iberiotoxin had a significant inhibitory effect in only one of these groups, the losartan-treated GK. The relaxations induced by the SKCa/IKCa activator NS309 and the BKCa activator NS1619, which were impaired in GK rats, were normalized by losartan treatment. We conclude that losartan improves EDHF-type relaxation in GK rats at least partly by normalizing SKCa/IKCa activities and increasing BKCa activity.
- 社団法人 日本薬理学会の論文
著者
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MATSUMOTO Takayuki
Departments of Laboratory Medicine, Ohashi and Omori Hospitals, School of Medicine, Toho University
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Ishida Keiko
Department of Bioresources Chemistry, Chiba University
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KAMATA Katsuo
Department of Pharmacology, School of Pharmacy, Hoshi University
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Kamata Katsuo
Department Of Pharmacology School Of Pharmacy Hoshi University:department Of Chemical Pharmacology F
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Ishida Keiko
Department Of Bioresources Chemistry Chiba University
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TAGUCHI Kumiko
Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University
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KOBAYASHI Tsuneo
Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University
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Matsumoto Takayuki
Department Of Physiology And Morphology Institute Of Medicinal Chemistry Hoshi University
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Kikuchi Toyohiko
Department Of Physiology And Morphology Institute Of Medicinal Chemistry Hoshi University
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Ishida Keiko
Department Of Physiology And Morphology Institute Of Medicinal Chemistry Hoshi University
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Kobayashi Tsuneo
Department Of Physiology And Morphology Institute Of Medicinal Chemistry Hoshi University
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Matsumoto Takayuki
Department Of Gastroenterology And Hepatology Institute Of Clinical Medicine Graduate School Of Comp
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Kobayashi Tsuneo
Department Of Physics School Of Medicine Fukushima Medical University
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Matsumoto Takayuki
Department Of Electronics Information And Communication Engineering Waseda University
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KAMATA Katsuo
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University
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Kamata Katsuo
Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Japan
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Taguchi Kumiko
Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Japan
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