Direct vasorelaxation by a novel phytoestrogen @entity16217 is mediated by nongenomic action of @entity172 receptor through endothelial XXXX synthase activation and calcium mobilization.

@entity172 @entity2508 @entity16217 @entity842 @entity35 @entity1299 @entity65
Salvia miltiorrhiza (Danshen) has been widely used in China and other Asian countries for treating various @entity65 resulting from its ability to improve coronary microcirculation and increase coronary blood flow. @entity16217 (Tan IIA), the major active lipophilic ingredient responsible for the beneficial actions of Salvia miltiorrhiza, has been shown to induce vasodilation in coronary arteries. Because our recent study identified Tan IIA as a new member of the phytoestrogens, we hypothesized that its action might be mediated by @entity172 receptor (ER) in vascular endothelial cells. The aim of the present study was to assess whether cardiovascular protection exerted by Tan IIA is mediated by the ER signal pathway and whether the genomic or nongenomic action of ER is involved within arteries and vascular endothelial cells. The effect of Tan IIA on blood vessels was investigated by vascular ring assay using endothelium-intact and endothelium-denuded @entity35 aortas. Similar to @entity172 , Tan IIA caused an @entity842 - and endothelium-dependent relaxation, which was blocked by ER antagonist @entity1299 . Primary cardiac microvascular endothelial cells were used as a model to study the cellular and molecular mechanisms of Tan IIA-induced vasorelaxation. We demonstrate that Tan IIA is capable of activating the @entity172 receptor signal pathway, leading to increased endothelial @entity842 synthase gene expression, @entity842 production, @entity2508 phosphorylation, and Ca mobilization. Collectively, these effects contribute to Tan IIA's vasodilative activity effects of y ER antagonist Cnt of @entity65 . Our findings support a continued effort in discovering and developing novel phytoestrogens as an alternative hormone replacement therapy for safer and more effective treatment of @entity65 .
