Losartan Normalizes Endothelium-Derived Hyperpolarizing Factor-Mediated Relaxation by Activating Ca2+-Activated K+ Channels in Mesenteric Artery From Type 2 Diabetic GK Rat

DOI Web Site 被引用文献6件 参考文献98件
  • Matsumoto Takayuki
    Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Japan
  • Ishida Keiko
    Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Japan
  • Taguchi Kumiko
    Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Japan
  • Kobayashi Tsuneo
    Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Japan
  • Kamata Katsuo
    Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Japan

この論文をさがす

抄録

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.

収録刊行物

被引用文献 (6)*注記

もっと見る

参考文献 (98)*注記

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ