PROPERTIES OF A PROGESTERONE-INDUCED RELAXATION IN HUMAN PLACENTAL ARTERIES AND VEINS

To study the effects of progesterone on placental vascular tone, we used isolated (1-2 mm in diameter) placental arteries and veins from term uncomplicated pregnancies. These vessels, incubated in Krebs buffer (pH 7.4) under 5% 0(2)-5% CO2 (balance N-2, PO2 similar to 35 torr) and precontracted with serotonin were exposed to incremental doses of progesterone (0.01-30 mu mol/L) in the presence or absence of endothelium, 10 mu mol/L indomethacin (inhibits prostaglandin synthesis), 10 mu mol/L, methylene blue (a soluble guanylate cyclase inhibitor), 100 mu mol/L nitro-L-arginine (inhibits L-arginine metabolism), 1 mmol/L isobutylmethylxanthine (a cAMP phosphodiesterase inhibitor), or 30 mu mol/L mifepristone (RU 38486, an antiprogestin). Progesterone elicited an acute dose-dependent relaxation in both arteries and veins that was not altered by removal of the endothelium or pretreatment with indomethacin, nitro-L-arginine, or methylene blue, excluding a role for prostaglandins, L-arginine products, or cGMP in mediating this relaxation. However, isobutylmethylxanthine significantly enhanced the relaxation in response to progesterone, suggesting a role for cAMP. RU 38486 inhibited the relaxation by 50-100%, depending on the progesterone dose, consistent with a role for progesterone receptors. These results suggest that progesterone causes a dose-dependent endothelium-independent relaxation of human placental arteries and veins. This relaxation seems to be mediated by a receptor-activated cAMP mechanism and could be physiologically important in maintaining low resistance and adequate blood now in the placental circulation.