Endothelium-dependent rhythmic contractions induced by cyclopiazonic acid in rat mesenteric artery.
The action of cyclopiazonic acid, the putative inhibitor of the Ca(2+)-ATPase of endoplasmic reticulum, on phenylephrine-evoked-isometric contractions in rat isolated mesenteric arteries were investigated. Cyclopiazonic acid (3 microM) 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 NG-nitro-L-arginine (100 microM) 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 NG-nitro-L-arginine (100 microM). 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 NG-nitro-L-arginine (100 microM). 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.
Huang
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Department of Physiology, Faculty of Medicine, Chinese University of Hong Kong, Shatin, NT, Hong Kong. b538708@mailserv.cuhk.edu.hk
Cheung
K K
KK
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D008638:Mesenteric Arteries / Q000187:drug effects*; D009119:Muscle Contraction / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D019335:Nitroarginine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism; D051381:Rats; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D007211:Indoles; D015221:Potassium Channels; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010656:Phenylephrine; D019335:Nitroarginine; D009543:Nifedipine; C000543:cyclopiazonic acid; D007213:Indomethacin