Abstract

We checked the hypothesis whether the non-classical estrogen receptor modulators genistein and raloxifene could affect platelet aggregation through their direct effect on vascular tissue by regulating the synthesis of vasoactive compounds. In rat aortic strips, 10 nM genistein or 10 nM raloxifene significantly increased nitric oxide synthesis, event prevented by ICI182780. Both agents exhibited an antiaggregatory action, dependent on the nitric oxide release from vascular tissue, since preincubation of aortic strips with l-NAME partially and completely suppressed the inhibition of platelet aggregation induced by genistein or raloxifene respectively. The phytoestrogen enhanced phospholipase A₂ and prostacyclin release into the incubation medium. Indomethacin reduced in half the inhibition of platelet aggregation elicited by genistein. Finally, genistein or raloxifene also inhibited platelet aggregation in aortic strips from ovariectomized rats. In conclusion, genistein and raloxifene exhibit an antiplatelet activity through their direct action on vascular tissue, in rats with or without ovarian activity.

Keywords: Genistein; Raloxifene; Platelet aggregation; Nitric oxide; Prostacyclin