Effects of cyclopiazonic acid on phenylephrine‐induced contractions in the rabbit ear artery

1 Upon stimulation with phenylephrine, the rabbit ear artery displays endothelium‐regulated rhythmic contractions, which may be attributed to the periodical activation of the dihydropyridine‐sensitive Ca2+ channel, presumably regulated by the Ca2+‐activated K+ channel. The effect of cyclopiazonic acid (CPA), an inhibitor of the Ca2+‐ATPase of the sarcoplasmic reticulum (SR), on phenylephrine‐induced contractions was examined in endothelium‐denuded rabbit ear arteries suspended in an organ chamber for isometric tension recordings. 2 Phenylephrine‐induced tonic contractions were converted to rhythmic ones by the addition of CPA. 3 The CPA‐induced rhythmic contractions were abolished by the blockade of the dihydropyridine‐sensitive Ca2+ channel and the Ca2+‐activated K+ channel by nifedipine and charybdotoxin, respectively. In contrast, glibenclamide, an ATP‐sensitive K+ channel antagonist, had no effect on the CPA‐induced rhythmic responses. 4 CPA attenuated both Ca2+ repletion by the SR and Ca2+ influx across the plasmalemma without having a significant effect on Ca2+ release from the SR, as evaluated by phenylephrine‐induced contractions. In contrast, these three parameters were not altered by the presence of the endothelium. 5 These findings indicate that the CPA‐induced rhythmic contractions in the endothelium‐denuded rabbit ear artery may be induced by the same ionic mechanism as endothelium‐regulated rhythmic responses, by which the K+ channel could regulate the probability of the Ca2+ channel being opened. The CPA‐induced rhythmic contractions may correlate with the inhibitory effects of CPA on the SR function, although this is not true for the endothelium‐regulated rhythmic contractions.