(+)-Praeruptorin A
(+)-Praeruptorin A exerts distinct relaxant effects on isolated rat aorta rings, which may be mainly attributed to nitric oxide synthesis catalyzed by endothelial nitric oxide synthase.
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Chem Biol Interact. 2010 Jul 30;186(2):239-46.
(+/-)-Praeruptorin A enantiomers exert distinct relaxant effects on isolated rat aorta rings dependent on endothelium and nitric oxide synthesis.[Pubmed:
20433815]
METHODS AND RESULTS:
(+)-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).
CONCLUSIONS:
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.
