(+/-)-Praeruptorin A enantiomers exert distinct relaxant effects on isolated rat aorta rings dependent on endothelium and nitric oxide synthesis.

Praeruptorin A is a coumarin compound naturally occurring in the roots of Peucedanum praeruptorum Dunn., a commonly used traditional Chinese medicine for the treatment of certain respiratory diseases and hypertension. Although previous studies indicated the relaxant effects of (+/-)-praeruptorin A on tracheal and arterial preparations, little is known about the functional characteristics of the enantiomers. In the present study, the two enantiomers were successfully isolated and identified by using a preparative Daicel Chiralpak AD-H column, and their relaxant effects on aorta rings were observed and compared. (+)-Praeruptorin A showed more potent relaxation than (-)-praeruptorin A against KCl- and phenylephrine-induced contraction of rat isolated aortic rings with intact endothelium. Removal of the endothelium remarkably reduced the relaxant effect of (+)-praeruptorin A but not that of (-)-praeruptorin A. Pretreatment of aortic rings with N(omega)-nitro-L-arginine methyl ester (L-NAME, an inhibitor of nitric oxide synthase) or methylene blue (MB, a soluble guanylyl cyclase inhibitor) resulted in similar changes of the relaxant effects of the two enantiomers to endothelium removal. Molecular docking studies also demonstrated that (+)-praeruptorin A was in more agreement to nitric oxide synthase pharmacophores than (-)-praeruptorin A. On the other hand, the two enantiomers of praeruptorin A could slightly attenuate the contraction of rat aortic rings induced by internal Ca(2+) release from sarcoplasmic reticulum (SR). These findings indicated that (+)-praeruptorin A and (-)-praeruptorin A exerted distinct relaxant effects on isolated rat aorta rings, which might be mainly attributed to nitric oxide synthesis catalyzed by endothelial nitric oxide synthase.

Xu Z ，Wang X ，Dai Y ，Kong L ，Wang F ，Xu H ，Lu D ，Song J ，Hou Z ... -  《-》

Endothelium dependence and gestational regulation of inhibition of vascular tone by magnesium sulfate in rat aorta.

Longo M ，Jain V ，Vedernikov YP ，Facchinetti F ，Saade GR ，Garfield RE ... -  《AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY》

Mechanism of UV light-induced photorelaxation in isolated rat aorta.

Kim JH ，Hong Y ，Shim CS 《-》

Impairment of smooth muscle function of rat thoracic aorta in an endothelium-independent manner by long-term administration of N(G)-nitro-L-arginine methyl ester.

López RM ，Ortíz CS ，Ruíz A ，Vélez JM ，Castillo C ，Castillo EF ... -  《FUNDAMENTAL & CLINICAL PHARMACOLOGY》

The direct effect of levobupivacaine in isolated rat aorta involves lipoxygenase pathway activation and endothelial nitric oxide release.

Choi YS ，Jeong YS ，Ok SH ，Shin IW ，Lee SH ，Park JY ，Hwang EM ，Hah YS ，Sohn JT ... -  《-》