The vascular activity of some isoflavone metabolites: implications for a cardioprotective role

Legume‐derived isoflavones such as genistein, diadzein and equol have been associated with a reduction in risk of cardiovascular disease. In the current study, we explore the vascular activity of several isoflavone metabolites namely dihydrodaidzein, cis and trans‐tetrahydrodaidzein and dehydroequol for potential cardioprotective properties. Rat isolated aortic rings were used. 17β‐oestradiol, equol, and all four of the metabolites studied significantly antagonized contractile responses to noradrenaline. The direct vasodilatory action of these compounds were examined and in contrast to 17β‐oestradiol, the vasodilatory effect of which was demonstrated to be endothelium independent, the dilatory action of all four compounds could be inhibited by endothelium denudation. Further, the dilatory action of both dihydrodaidzein and cis‐tetrahydrodaidzein were inhibited by the nitric oxide synthase inhibitor, Nω‐nitro‐L‐arginine (NOLA), by the soluble guanylate cyclase inhibitor, 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ) and by 40 mM KCl. Dilatory responses to dehydroequol and trans‐tetrahydrodaidzein, on the other hand, were inhibited by 40 mM KCL but not by NOLA nor ODQ. Finally, we examined the protective potential of these compounds in inhibiting endothelium damage by oxidized low density lipoprotein (ox‐LDL). Trans‐tetrahydrodaidzein was at least 10 fold more potent than 17β‐oestradiol in protecting against ox‐LDL induced damage. We conclude that the isoflavone metabolites, dihydrodaidzein, cis‐ and trans‐tetrahydrodaidzein and dehydroequol, may potentially represent a novel series of cardioprotective therapeutics. British Journal of Pharmacology (2001) 133, 595–605; doi:10.1038/sj.bjp.0704088