HORMONE REPLACEMENT THERAPY MODIFIES THE CAPACITY OF PLASMA AND SERUMTO REGULATE PROSTACYCLIN AND ENDOTHELIN-1 PRODUCTION IN HUMAN VASCULAR ENDOTHELIAL-CELLS

Objective: To determine if hormone replacement therapy (HRT) modifies the ability of plasma or serum to regulate the synthesis of vasodilato ry prostacyclin and that of vasoconstrictive endothelin-1 by cultured human umbilical vein endothelial cells. Design: Plasma and serum colle cted before and during the sixth treatment cycle of HRT from 13 health y postmenopausal women were added to cultured endothelial cells. Setti ng: Helsinki University Central Hospital, Department of Obstetrics and Gynecology, Helsinki, Finland. Patients: Thirteen postmenopausal wome n(greater than or equal to 1 year since their last menstruation, FSH l evel > 40 mIU/mL [conversion factor to SI unit, 1.00], clear vasomotor symptoms) that suffered from incapacitating menopausal symptoms neces sitating the initiation of HRT were studied. Interventions: A combined regimen consisting of 2 mg oral E(2) for 12 days followed by 2.0 mg o ral E(2) + 1.0 mg norethisterone acetate for 10 days and 1.0 mg E(2) f or 6 days. Main Outcome Measures: The releases of prostacyclin, as ass essed by its metabolite 6-keto-prostaglandin F-1 alpha, and that of en dothelin-1 by cultured human umbilical vein endothelial cells in the p resence of 10% plasma or 10% serum collected from the study subjects. Results: Hormone replacement therapy enhanced the ability of plasma to stimulate prostacyclin production by 21% + 6% (mean +/- SEM) during t he E(2) + norethisterone acetate phase and tended to do so also during the E(2)-only phase (11% +/- 10%) but caused no change in endothelin- 1 release. In contrast, HRT decreased the ability of serum to stimulat e prostacyclin production by 12% +/- 5% during the E(2)-only phase and increased that of endothelin-1 by 8% +/- 4% during the E(2) + norethi sterone acetate phase. Conclusion: Because plasma flushes endothelial cells in vivo, our data on the HRT-induced stimulation of the capacity of plasma to enhance the production of vasoprotective prostacyclin wi thout a concomitant change in endothelin-1 release in cultured human u mbilical vein endothelial cells may provide one new explanation for th e cardiovascular protection of HRT.