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% O2-5% CO2 (balance N2, PO2 approximately 35 torr) and precontracted with serotonin were exposed to incremental doses of progesterone (0.01-30 mumol/L) in the presence or absence of endothelium, 10 mumol/L indomethacin (inhibits prostaglandin synthesis), 10 mumol/L methylene blue (a soluble guanylate cyclase inhibitor), 100 mumol/L nitro-L-arginine (inhibits L-arginine metabolism), 1 mmol/L isobutylmethylxanthine (a cAMP phosphodiesterase inhibitor), or 30 mumol/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 flow in the placental circulation.
Department of Pediatrics, West Virginia University, Morgantown 26506.
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D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001158:Arteries / Q000187:drug effects; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008751:Methylene Blue / Q000494:pharmacology; D015735:Mifepristone / Q000494:pharmacology; D019335:Nitroarginine; D010920:Placenta / Q000098:blood supply*; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects; D014666:Vasomotor System / Q000187:drug effects; D014680:Veins / Q000187:drug effects
D019335:Nitroarginine; D015735:Mifepristone; D011374:Progesterone; D001120:Arginine; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D008751:Methylene Blue; D007213:Indomethacin