Rhythmic relaxations of active tension in the rabbit large arteries induced by a combination of cyclopiazonic acid and Bay K 8644.
1. We previously demonstrated that cyclopiazonic acid (CPA), an inhibitor of Ca(2+)-ATPase in the sarcoplasmic reticulum, induced rhythmic relaxations of active tension in the endothelium-denuded small arteries of the mesentery and the ear of the rabbit, but that this agent failed to induce rhythmic responses in the endothelium-denuded rabbit femoral artery. 2. In the present study, an attempt was made to induce rhythmic relaxations of active tension in the endothelium-denuded rabbit femoral artery and the thoracic aorta, both of which were suspended in organ chambers for isometric tension recordings, by using CPA plus Bay K 8644, an L-type Ca2+ channel agonist, to induce an excessive increase in cytosolic Ca2+. 3. CPA or Bay K 8644 alone failed to produce rhythmic relaxations in the femoral artery that had been contracted with phenylephrine. In contrast, rhythmic responses were induced by the sequential treatment of the femoral artery with CPA and Bay K 8644. 4. The rhythmic relaxations of active tension in the femoral artery induced by CPA plus Bay K 8644 were inhibited by charybdotoxin and by iberiotoxin, both of which are antagonists of the Ca(2+)-activated K+ channel, but not by glibenclamide, a blocker of the ATP-sensitive K+ channel. 5. The endothelium-denuded rabbit aorta also exhibited rhythmic responses by the sequential addition of CPA and Bay K 8644. These responses were sensitive to charybdotoxin. 6. These findings indicate that, like small arteries, the large femoral and aortic arteries of the rabbit are also capable of displaying rhythmic relaxations of active tension; these relaxations may be in part attributed to the activation of the Ca(2+)-activated K+ channel as a result of the Ca2+ overload caused by CPA and Bay K 8644.
Omote
M
M
Marion Merrell Dow, Osaka, Japan.
Mizusawa
H
H
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001158:Arteries / Q000187:drug effects* / Q000502:physiology; D002120:Calcium Channel Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D005263:Femoral Artery / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D011817:Rabbits; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D002120:Calcium Channel Agonists; D004791:Enzyme Inhibitors; D007211:Indoles; D014665:Vasodilator Agents; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C000543:cyclopiazonic acid