title: Estrogen and postmenopausal estrogen/progestin therapy: effect on endothelium-dependent prostacyclin, nitric oxide and endothelin-1 production.
abstract: It is well documented that postmenopausal estrogen/progestin therapy (HRT) protects women against cardiovascular disorders. However, the mechanism(s) by which this protection is mediated remains largely unresolved, because beneficial effects of estrogen on the blood lipid profile account for only 20-30% of the overall protection. Growing evidence suggests that estrogen has direct effects on the blood vessel wall indicating that vascular endothelium may play a key role in mediating these effects by producing vasoactive factors, such as prostacyclin (PGI2), nitric oxide (NO) and endothelin-1 (ET-1). In vitro estrogen stimulates endothelial PGI2 and NO production, whereas ET-1 production is not affected. Moreover, in vivo studies indicate that estrogen and HRT increase PGI2 and NO production, whereas ET-1 production decreases. These effects are evidently mediated through estrogen receptors in endothelial cells. Thus, estrogen and HRT lead to the dominance of vasodilatory and antiaggregatory agents released by the endothelial cells. This may be an important new mechanism in the cardiovascular protection mediated by estrogen and HRT.
authors.affiliation: Department of Obstetrics and Gynaecology, Helsinki University Central Hospital, Finland.
authors.forename: T
authors.initials: T
authors.lastname: Mikkola
authors.forename: L
authors.initials: L
authors.lastname: Viinikka
authors.forename: O
authors.initials: O
authors.lastname: Ylikorkala
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004359:Drug Therapy, Combination; D019332:Endothelin-1 / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis*; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000096:biosynthesis*; D011372:Progestins / Q000627:therapeutic use*
chemical_list: D019332:Endothelin-1; D011372:Progestins; D009569:Nitric Oxide; D011464:Epoprostenol