title: Effect of 17beta-estradiol on inhibition of platelet aggregation in vitro is mediated by an increase in NO synthesis.
abstract: The low prevalence of coronary heart disease in premenopausal women and its increase after menopause are well established. Although estrogen is thought to play a role in protecting the vasculature, the mechanism has not been fully clarified. The contribution of platelets to atherosclerotic cardiovascular diseases is well recognized. The present study focused on the still-controversial effect of estrogen on platelet function. We investigated the in vitro effects of estrogen on human platelets, including their aggregation, Ca2+ metabolism, the synthesis of cyclic nucleotides, and NO (nitrite/nitrate) synthesis after stimulation with thrombin or ADP. Pretreatment of platelets with 17beta-estradiol reduced the platelet aggregation induced by thrombin or ADP, whereas 17alpha-estradiol had no effect. 17Beta-estradiol accelerated the recovery of [Ca2+]i after the agonist-induced peak and reduced the area under the curve of accumulated platelet [Ca2+]i but did not alter the baseline [Ca2+]i, Ca2+ influx induced by thrombin or ADP, the release of Ca2+ from internal stores, or the size of internal Ca2+ stores. Pretreatment of platelets with 17beta-estradiol had no effect on the intracellular concentration of cAMP but increased that of cGMP in agonist-stimulated platelets. Additionally, 17beta-estradiol increased the platelet concentration of nitrite/nitrate in a dose-dependent manner. These effects of 17beta-estradiol on platelet aggregation, Ca2+ metabolism, and NO synthesis were abolished by exposure to N(G)-monomethyl-L-arginine, an NO synthesis inhibitor. These results suggest that 17beta-estradiol plays an important role in inhibiting platelet aggregation by promoting Ca2+ extrusion or reuptake activity that is dependent on the production of cGMP by increasing NO synthesis.
authors.affiliation: Department of Clinical Laboratory Medicine, Hiroshima University School of Medicine, Japan. nakano@mcai.med.hiroshima-u.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Nakano
authors.forename: T
authors.initials: T
authors.lastname: Oshima
authors.forename: H
authors.initials: H
authors.lastname: Matsuura
authors.forename: G
authors.initials: G
authors.lastname: Kajiyama
authors.forename: M
authors.initials: M
authors.lastname: Kambe
mesh_terms: D000328:Adult; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D010975:Platelet Aggregation Inhibitors; D009569:Nitric Oxide; D004958:Estradiol; D000242:Cyclic AMP; D006152:Cyclic GMP; D002118:Calcium