Effect of 17beta-estradiol on inhibition of platelet aggregation in vitro is mediated by an increase in NO synthesis.
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.
Nakano
Y
Y
Department of Clinical Laboratory Medicine, Hiroshima University School of Medicine, Japan. nakano@mcai.med.hiroshima-u.ac.jp
Oshima
T
T
Matsuura
H
H
Kajiyama
G
G
Kambe
M
M
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*
D010975:Platelet Aggregation Inhibitors; D009569:Nitric Oxide; D004958:Estradiol; D000242:Cyclic AMP; D006152:Cyclic GMP; D002118:Calcium