Effects of equine oestrogens on markers of vasoactive function in human coronary artery endothelial cells.
A large proportion of the beneficial effects that oestrogens demonstrate on the vasculature are believed to be mediated via direct effects on the vascular wall. In this study we compared a number of oestrogenic compounds isolated from pregnant mare's urine including 17beta-oestradiol and oestrone, in terms of their abilities to inhibit stimulated endothelin-1 release from normal human coronary artery endothelial cells (CAEC). We also examined their ability to stimulate expression of constitutive endothelial nitric oxide synthase (eNOS) and explored their effects on cellular angiotensin converting enzyme (ACE). All the oestrogens tested were able to inhibit serum-stimulated ET-1 release. Oestrone and 17alpha-dihydroequilenin failed to significantly affect cellular eNOS levels. 17Beta-oestradiol and oestrone significantly increased cellular ACE levels while 17beta,delta(8,9)-dehydroestradiol decreased cellular ACE. We discuss these observations in terms of their potential clinical relevance and use as a means of screening novel oestrogen-like compounds.
Wynn Department of Metabolic Medicine, Endocrinology and Metabolic Medicine, Imperal College School of Medicine, St. Mary's Medical School, London, UK. c.wingrove@ic.ac.uk
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D000818:Animals; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000502:physiology; D019332:Endothelin-1 / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000502:physiology*; D004855:Equilenin / Q000031:analogs & derivatives / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D004970:Estrone / Q000494:pharmacology*; D005260:Female; D006801:Humans; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052250:Nitric Oxide Synthase Type III; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis*; D011247:Pregnancy
D019332:Endothelin-1; C037874:17-dihydroequilenin; D004970:Estrone; D004958:Estradiol; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D007703:Peptidyl-Dipeptidase A; D004855:Equilenin