Effect of genistein and raloxifene on vascular dependent platelet aggregation.
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, 10nM genistein or 10nM 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 A(2) 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.
Polini
Nélida
N
Cátedra de Análisis Clínicos II, Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, San Juan 670, B8000ICN Bahía Blanca, Buenos Aires, Argentina.
Rauschemberger
María Belén
MB
Mendiberri
Josefina
J
Selles
Juana
J
Massheimer
Virginia
V
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects*; D015777:Eicosanoids / Q000096:biosynthesis; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D019833:Genistein / Q000494:pharmacology*; D066298:In Vitro Techniques; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010052:Ovariectomy; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology
D000970:Antineoplastic Agents; D015777:Eicosanoids; D010975:Platelet Aggregation Inhibitors; D020845:Selective Estrogen Receptor Modulators; D000077267:Fulvestrant; D009569:Nitric Oxide; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D000244:Adenosine Diphosphate; D019833:Genistein; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester