title: (+/-)-Praeruptorin A enantiomers exert distinct relaxant effects on isolated rat aorta rings dependent on endothelium and nitric oxide synthesis.
abstract: 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.
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, Jiangsu, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Xu
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Wang
authors.forename: Yue
authors.initials: Y
authors.lastname: Dai
authors.forename: Lingyi
authors.initials: L
authors.lastname: Kong
authors.forename: Fengyun
authors.initials: F
authors.lastname: Wang
authors.forename: Huan
authors.initials: H
authors.lastname: Xu
authors.forename: Dan
authors.initials: D
authors.lastname: Lu
authors.forename: Jie
authors.initials: J
authors.lastname: Song
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Hou
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology*; D020013:Calcium Signaling / Q000187:drug effects; D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D003374:Coumarins; D004365:Drugs, Chinese Herbal; D008024:Ligands; D014665:Vasodilator Agents; C441070:praeruptorin A; D010656:Phenylephrine; D009569:Nitric Oxide; D011189:Potassium Chloride; D006152:Cyclic GMP; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester