Cilostamide produces hyperpolarization associated with katp channel activation, but does not augment endothelium-derived hyperpolarization in rat mesenteric arteries

Yasuo Kansui, Kenichi Goto, Koji Fujii, Hideyuki Oniki, Kiyoshi Matsumura, Mitsuo Iida

研究成果: Contribution to journalArticle査読

2 被引用数 (Scopus)

抄録

Non-nitric oxide/prostaglandin-mediated endothelium-derived hyperpolarization (EDH) is considered to be mediated, in part, by gap junctions and it has been suggested that cAMP increases endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation through the modulation of gap junctions. Cilostamide, which inhibits phosphodiesterase III, has been suggested to augment EDHF-type relaxation by increasing the concentration of cAMP. In the present study, we investigated the effect of cilostamide on EDH per se in mesenteric arteries of Wistar rats using a conventional microelectrode technique. The resting membrane potential of the mesenteric arteries was significantly more negative in the presence of 10-6 mol/L cilostamide compared with control conditions. Furthermore, EDH in response to 10 -6 mol/L acetylcholine (ACh) in the presence of 10-5 mol/L indomethacin and 10-4 mol/L NG-nitro-L-arginine was decreased in the presence of 10-6 mol/L cilostamide by approximately 5 and 3.5 mV in proximal and distal arteries, respectively. Glibenclamide (10-5 mol/L), an ATP-sensitive potassium channel (KATP) inhibitor, abolished the hyperpolarization to 10-6 mol/L cilostamide. Furthermore, in the presence of glibenclamide, ACh-induced EDH was unaffected by cilostamide, suggesting that the inhibition of ACh-induced hyperpolarization by cilostamide in the absence of glibenclamide may be due to the smaller driving force for hyperpolarization because of the more negative membrane potential under such conditions. The findings of the present study suggest that cilostamide produces hyperpolarization by activating KATP channels, presumably by increasing cAMP. However, cilostamide alone may not directly affect EDH.

本文言語英語
ページ(範囲)729-733
ページ数5
ジャーナルClinical and Experimental Pharmacology and Physiology
36
7
DOI
出版ステータス出版済み - 7 2009

All Science Journal Classification (ASJC) codes

  • 生理学
  • 薬理学
  • 生理学(医学)

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