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 receptor-mediated, cAMP-dependent relaxation in isolated placental arteries and veins from normal term pregnancies that may be important in maintaining adequate blood flow in the placental circulation. Objective: To further investigate the activity of progesterone and some of its metabolites in both placental and umbilical vessels. Study design: Isolated human placental and umbilical arteries and veins from normal term pregnancies, incubated in Krebs-bicarbonate buffer and submaximally precontracted with potassium chloride, were exposed to cumulative concentrations (0.01-30 µm) of progesterone, 5beta-pregnane-3,20-dione, 5alpha-pregnane-3,20-dione, or 5alpha-pregnane-3beta-ol-20-one. Results: All experimental progestins produced concentration-dependent relaxations in precontracted human placental and umbilical arteries and veins. These relaxations were endothelium-independent. Progesterone and 5beta-pregnane-3,20-dione appeared to be the most potent and efficient of the tested progestins, whereas 5alpha-pregnane-3beta-ol-20-one produced the least relaxation in the same vessels. Conclusions: These results suggest that not only progesterone, but also its metabolites, may be of physiological importance in the regulation of umbilico-placental vascular tone. Additionally, it appears that the umbilical blood vessels possess the same relaxation to progesterone as placental arteries and veins. Taken together, these results indicate a potential role for progesterone and its metabolites in maintaining adequate blood flow in the umbilico-placental circulation.