Mechanisms underlying the vasorelaxing effects of butylidenephthalide, an active constituent of Ligusticum chuanxiong, in rat isolated aorta.

Butylidenephthalide (BDPH) is one of the most potent vasorelaxants isolated from Ligusticum chuanxiong Hort. The objective of the current study is to investigate the underlying vasorelaxation mechanisms in rat aorta. In 9,11-dideoxy-9alpha,11alpha-methanoepoxyprostaglandin F(2alpha) (U46619) precontracted preparations, endothelium removal, the nitric oxide (NO) synthase inhibitor Nomega-nitro-l-arginine methyl ester (l-NAME) and the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) partially inhibited the BDPH relaxation response to a similar extent. The cyclooxygenase inhibitor indomethacin, beta-adrenoceptor antagonist propranolol, adenylate cyclase inhibitors 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ 22536) and 2',5'-dideoxyadenosine, and K(+) channel blocker tetraethylammonium had no effect. BDPH produced full relaxation against contractions induced by KCl and U46619 in the presence of the l-type voltage-operated Ca(2+) channel (Ca(v) 1.2) blocker nifedipine. In a receptor-operated Ca(2+) channel protocol where contraction was mediated by Ca(2+) re-addition in the presence of U46619 and nifedipine, BDPH produced relaxation. In the absence of extracellular Ca(2+), BDPH inhibited contractions induced by phorbol-12,13-dibutyrate and U46619. Our results suggest that BDPH-mediated vasorelaxation comprises both endothelium-dependent (NO) and independent components. It is suggested that BDPH acting through an inhibitory mechanism downstream to l-type voltage-operated and prostanoid TP receptor-operated Ca(2+) channels operating late in the contractile pathway.