IN-VITRO VASCULAR RELAXATION TO PROGESTERONE AND ITS METABOLITES IN HUMAN UMBILICAL AND PLACENTAL BLOOD-VESSELS

Background: We have recently reported that progesterone caused a recep tor-mediated, cAMP-dependent relaxation in isolated placental arteries and veins from normal term pregnancies that may be important in maint aining adequate blood flow in the placental circulation. Objective: To further investigate the activity of progesterone and some of its meta bolites in both placental and umbilical vessels. Study design: Isolate d human placental and umbilical arteries and veins from normal term pr egnancies, incubated in Krebs-bicarbonate buffer and submaximally prec ontracted with potassium chloride, were exposed to cumulative concentr ations (0.01-30 mu M) of progesterone, 5 beta-pregnane-3,20-dione, 5 a lpha-pregnane-3,20-dione, or 5 alpha-pregnane-3 beta-ol-20-one. Result s: All experimental progestins produced concentration-dependent relaxa tions in precontracted human placental and umbilical arteries and vein s. These relaxations were endothelium-independent. Progesterone and 5 beta-pregnane-3,20-dione appeared to be the most potent and efficient of the tested progestins, whereas 5 alpha-pregnane-3 beta-ol-20-one pr oduced the least relaxation in the same vessels. Conclusions: These re sults suggest that not only progesterone, but also its metabolites, ma y be of physiological importance in the regulation of umbilico-placent al vascular tone. Additionally, it appears that the umbilical blood ve ssels possess the same relaxation to progesterone as placental arterie s and veins. Taken together, these results indicate a potential role f or progesterone and its metabolites in maintaining adequate blood flow in the umbilico-placental circulation.