The vasorelaxation effect of osthole, derived from radix angelicae pubescentis, in porcine coronary artery

Abstract

Radix Angelicae Pubescentis is a traditional Chinese medicine used to treat thrombosis. Osthole, a coumarin from Angelica pubescens, possesses antiarrhythmic activity. The vascular effects of Angelica pubescens extract (APE) and osthole, as well as their underlying signaling pathways, were investigated in isolated porcine coronary artery rings contracted with U46619.

APE (20–80 μg/ml) dose-dependently relaxed endothelium-intact and endothelium-disrupted arterial rings to a similar extent. Osthole induced relaxation in endothelium-intact rings with a lower threshold concentration (< 10 μM) than in endothelium-disrupted rings (> 10 μM). In the presence of L-NAME (a nitric oxide synthase inhibitor) or ODQ (a soluble guanylyl cyclase inhibitor), relaxation to osthole in endothelium-intact rings was similar to that in endothelium-disrupted rings. Neither APE- nor osthole-induced relaxation was inhibited by SQ22536 (an adenylyl cyclase inhibitor).

Our results demonstrated that APE acted directly on vascular smooth muscle to induce relaxation, whereas osthole acted on both endothelium and smooth muscle for relaxation. The endothelium-dependent relaxation of osthole was mediated through nitric oxide-cGMP signaling cascade. Mechanisms other than cAMP signaling pathway appeared to be responsible for endothelium-independent relaxation effect of APE and osthole.