Endothelium-dependent rhythmic contractions induced by cyclopiazonic acid, a sarcoplasmic reticulum Ca(2+)-pump inhibitor, in the rabbit femoral artery.
The vascular responses to cyclopiazonic acid (CPA), an inhibitor of the Ca(2+)-ATPase in the sarcoplasmic reticulum, were investigated in the rabbit femoral artery, suspended in an organ chamber for isometric tension recordings. CPA produced rhythmic contractions in the femoral artery which had been contracted with phenylephrine. CPA, however, did not induce the rhythmic responses in endothelium-denuded arteries. NG-nitro-L-arginine methyl ester and methylene blue, inhibitors of the formation and the action of nitric oxide, respectively, failed to antagonize the CPA-induced rhythmic contractions in the phenylephrine-contracted artery. In contrast, the CPA-induced rhythmic contractions were abolished by charybdotoxin, a Ca(2+)-activated K+ channel antagonist, but not by glibenclamide, a blocker of the ATP-sensitive K+ channel. Nifedipine also inhibited the CPA-induced rhythmic contractions in the endothelium-intact artery and relaxed the endothelium-denuded artery treated with CPA. These results indicate that the CPA-induced rhythmic contractions in the phenylephrine-contracted rabbit femoral artery may be attributed to the periodic inactivation of the voltage-dependent Ca2+ channel, presumably regulated by the Ca(2+)-activated K+ channel. The activation of the K+ channel by CPA might occur only when the endothelium is present.
Omote
M
M
Marion Merrell Dow, Osaka, Japan.
Mizusawa
H
H
D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005263:Femoral Artery / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D015221:Potassium Channels / Q000502:physiology; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000187:drug effects
D015220:Calcium Channels; D007211:Indoles; D015221:Potassium Channels; D009569:Nitric Oxide; D000252:Calcium-Transporting ATPases; C000543:cyclopiazonic acid