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
Year1997
Month8
Day6
Volume Number332
Issue Number2
PublisherELSEVIER SCIENCE BV
Pages167 - 172
ISSN0014-2999
eISSN1879-0712
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