Endothelium-dependent rhythmic contractions induced by cyclopiazonic acid in rat mesenteric artery
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AbstractThe action of cyclopiazonic acid, the putative inhibitor of the Ca2+-ATPase of endoplasmic reticulum, on phenylephrine-evoked isometric contractions in rat isolated mesenteric arteries were investigated. Cyclopiazonic acid (3 mu M) induced an initial relaxation followed by rhythmic contractions of the phenylephrine-precontracted arteries with intact endothelium. Removal of endothelium abolished the effect of cyclopiazonic acid. Pretreatment of tissues with N-G-nitro-L-arginine (100 mu M) abolished the initial relaxation but not the rhythmic contractions. Indomethacin and glibenclamide did not affect the cyclopiazonic acid-induced response. Charybdotoxin (100 nM) converted the cyclopiazonic acid-induced rhythmic contractions to the sustained tension in the absence or presence of N-G-nitro-L-arginine (100 mu M). Pretreatment of charybdotoxin (100 nM) abolished cyclopiazonic acid-induced rhythmic activity but not the initial relaxation. Nifedipine (10 nM) abolished the effect of cyclopiazonic acid. Moderate increase of extracellular K+ (20 mM) reduced the initial relaxation but completely abolished rhythmic contractions induced by cyclopiazonic acid. The remaining relaxation was reversed or prevented by N-G-nitro-L-arginine (100 mu M). The results of the present investigation indicate that cyclopiazonic acid caused endothelium-dependent response in rat isolated mesenteric arteries probably by releasing nitric oxide responsible for the initial relaxation, and probably by releasing endothelium-derived hyperpolarizing factors primarily responsible for activation of charybdotoxin-sensitive K+ channels and induction of rhythmic contractile activity. (C) 1997 Elsevier Science B.V.
All Author(s) ListHuang Y, Cheung KK
Journal nameEuropean Journal of Pharmacology
Volume Number332
Issue Number2
Pages167 - 172
LanguagesEnglish-United Kingdom
Keywordscontractions, rhythmic; cyclopiazonic acid; endothelium; K+ channel; mesenteric artery, rat; nitric oxide (NO)
Web of Science Subject CategoriesPharmacology & Pharmacy; PHARMACOLOGY & PHARMACY

Last updated on 2020-12-10 at 01:08