Caffeine and nicotine: Effects on human placental vascular tone in vitro

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 F-2 alpha 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.