ABSTRACT
> 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.
ABSTRACT
>Objective: To investigate if the adverse effects caffeine and nicotine have on the fetus are mediated by placental vascular tone alterations.Study Design: Isolated human placental arteries and veins at resting tone in the presence and absence of endothelium were exposed to cumulative doses of caffeine (0.1 nm-0.1 mm), nicotine, and cotinine (1.0 nm-1.0 mm). Some of the vessels were submaximally precontracted with U44619 prior to exposure to cumulative doses of the drugs. Dose-response curves to serotonin, KCl, U46619, and prostaglandin F2alpha were also obtained in the presence or absence of caffeine, nicotine, and cotinine (0.1 mm).Results: Caffeine did not alter vascular tone in human placental arteries and veins at resting tone (n = 10). Modest relaxations (15-30% of maximal tone) were noted with the addition of the drug to precontracted placental blood vessels. Similarly, nicotine and cotinine had no effect on resting tone in placental blood vessels, whereas small relaxations (6-10% of maximal tone) occurred in vessels precontracted with U46619 (n = 7-10). Additionally caffeine (n = 6-10), nicotine, and cotinine failed to alter the dose-response curves to other contractile agents (n = 7-10).Conclusions: Based on these results caffeine, nicotine, and the nicotine metabolite cotinine do not appear to alter human placental vascular tone in vitro. These results suggest that the adverse effects of these drugs on the fetus during pregnancy are unlikely to be due to changes in placental vascular tone.
