Effect of butylidenephthalide on calcium mobilization in isolated rat aorta

Butylidenephthalide (Bdph), an antispasmodic compound originally isolated f rom the rhizome of Ligusticum chuaxiong, has a selective anti-anginal effec t without changing blood pressure. Experiments have been performed to deter mine the mechanism of this action. Synthetic Z-butylidenephthalide concentration-dependently relaxed phenyleph rine (1 mu M)- or KCl (60 mM)-induced precontractions of intact and denuded rat aorta rings. The relaxation induced by Bdph was endothelium-independen t. Bdph (30-300 mu M) concentration-dependently reduced cumulative phenylep hrine- and KCl-induced contractions of intact rat aortic rings and non-comp etitively inhibited their log concentration-response curves. The pD(2)' val ues of Bdph for phenylephrine- and KCl-induced contraction were 3.66 +/- 0. 13 (n = 8) and 3.71 +/- 0.07 (n = 8), respectively, which were not signific antly different from each other. Bdph also concentration-dependently reduce d cumulative Ca(2+)induced contractions of intact rat aortic rings in high- KCl (60 mM) Ca2+-free physiological salt solution and non-competitively inh ibited its log concentration-response curve. The pD(2)' value of Bdph for t he Ca2+-induced contractions was 3.21 +/- 0.01 (n = 7) which was significan tly different from the pD(2)' value obtained from the cumulative KCl-induce d contractions. These results suggest that Bdph inhibits calcium release from calcium store s more selectively than calcium influx from extracellular space via voltage -dependent calcium channels. The inhibition by Bdph of calcium release from KCl-sensitive calcium stores might be similar to its inhibition of calcium release from phenylephrine-sensitive calcium stores. However, because phen ylephrine generates inositol-1,4,5-trisphosphate (IP3) whereas KCl does not , the inhibitory effect of Bdph might not be related to IP3 production.