© 1998 American Heart Association, Inc.
Original Contributions |
Effect of 17ß-Estradiol on Inhibition of Platelet Aggregation In Vitro Is Mediated by an Increase in NO Synthesis
From the Department of Clinical Laboratory Medicine (Y.N., T.O., M.K.) and the First Department of Internal Medicine (H.M., G.K.), Hiroshima University School of Medicine, Hiroshima, Japan.
Correspondence to Yukiko Nakano, MD, Department of Clinical Laboratory Medicine, Hiroshima University School of Medicine, 1–2-3 Kasumi, Minami-ku, Hiroshima 734, Japan. E-mail nakano{at}mcai.med.hiroshima-u.ac.jp
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 17ß-estradiol reduced the platelet aggregation induced by
thrombin or ADP, whereas 17
-estradiol had no effect. 17ß-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 17ß-estradiol had no effect on the
intracellular concentration of cAMP but increased that of cGMP in
agonist-stimulated platelets. Additionally, 17ß-estradiol
increased the platelet concentration of nitrite/nitrate in a
dose-dependent manner. These effects of 17ß-estradiol on platelet
aggregation, Ca2+ metabolism, and NO synthesis
were abolished by exposure to
NG-monomethyl-L-arginine,
an NO synthesis inhibitor. These results suggest that
17ß-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.
Key Words: 17ß-estradiol • platelet aggregation • c GMP • nitric oxide • intracellular Ca2+
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