Pharmacological profile of phytoestrogens in cerebral vessels: in vitro study with rabbit basilar artery

As a previous step to consider their use in the pharmacology for stroke, we investigated the effects of four phytoestrogens (i.e. genistein, daidzein, zearalanone and biochanin A) on cerebral vessels. Cerebral vascular responses were analyzed by conventional recording of isometric tension in rabbit basilar artery segments kept in organ bath under standard conditions. The four phytoestrogens elicited concentration-dependent relaxant responses of different potency in basilar artery segments previously contracted with either 5x10(-2) M KCl or 10(-4) M UTP. Neither endothelium removal, 10(-4) M N(omega)-nitro-L-arginine methyl ester (L-NAME, nitric oxide (NO) synthase inhibitor), 10(-5) M1 H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, selective inhibitor of NO-sensitive guanylyl cyclase), 10(-5) M 4H-8-bromo-1,2,4-oxadiazolo(3,4-d)benz(b)(1,4)oxazin-1-one (NS2028, specific soluble guanylyl cyclase inhibitor), nor 10(-5) M indomethacin (prostaglandin biosynthesis inhibitor) modified the phytoestrogen-elicited vasorelaxant responses. On the other hand, Ca(2+)-elicited contractile responses were effectively inhibited in the presence of phytoestrogens. Phytoestrogens act as cerebrovascular relaxants by a mechanism which involves Ca(2+) entry blockade in the vascular smooth muscle rather than stimulation of vasorelaxant endothelium-related mechanisms such as NO/cGMP or prostaglandins.