Estrogen increases endothelial nitric oxide by a receptor-mediated system.
To determine the mechanism of the antiatherosclerotic effect of estrogen, we investigated the effect of estrogen on endothelial nitric oxide synthase (NOS-3). Preincubation with a physiologic concentration of 17 beta-estradiol (10(-12)-10(-8) M) over 8 hours significantly enhanced the activity of NOS-3 in endothelial cells of cultured human umblical vein (HUVEC) and of bovine aortas (BAEC). 17 beta-estradiol also enhanced the release of nitric oxide (NO) as measured by an NO selective meter and NO2-/NO3-, metabolites of NO, from endothelial cells. Western blot showed a similar effect of 17 beta-estradiol on NOS-3. The estrogen receptor antagonists, tamoxifen and ICI182780, each inhibited the effect of 17 beta-estradiol by 80%. The effect of 17 beta-estradiol gradually decreased in cells beyond the 10th passage and was not significant in cells beyond the 16th passage. Immunocytochemistry showed the existence of estrogen receptor in HUVEC and BAEC (less than 5 passages) and the sparseness of the existence in BAEC beyond the 16th passage. Estrogen increases NOS-3 via a receptor-mediated system, and estrogen receptor, which appeared to be altered by cell senescence, could be important in the release of NO from endothelium.
Hayashi
T
T
Department of Geriatrics, Nagoya University School of Medicine, Japan.
Yamada
K
K
Esaki
T
T
Kuzuya
M
M
Satake
S
S
Ishikawa
T
T
Hidaka
H
H
Iguchi
A
A
D000818:Animals; D001011:Aorta; D015153:Blotting, Western; D002417:Cattle; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D000077267:Fulvestrant; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D009566:Nitrates / Q000032:analysis; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000502:physiology*; D013629:Tamoxifen / Q000494:pharmacology; D014471:Umbilical Veins
D004965:Estrogen Antagonists; D007527:Isoenzymes; D009566:Nitrates; D011960:Receptors, Estrogen; D013629:Tamoxifen; D000077267:Fulvestrant; D009569:Nitric Oxide; D004958:Estradiol; D019001:Nitric Oxide Synthase