We have examined the contractile response to the vasoconstrictor endothelin-1 (ET-1) in uteroplacental arteries from normal pregnant women in the presence and absence of specific ET-receptor antagonists and agonists, and the vasodilator nitric oxide. Segments of placental arteries (n = 97) obtained from 37 placentas immediately after delivery were mounted in organ baths superfused with Krebs-Ringer solution at 37 degrees C. The tension was recorded isometrically and registered on a polygraph. We found that the placental artery segments responded to ET with a dose-dependent vasoconstriction. Half-maximal response was obtained at 2.6 x 10(-8) M. At 10(-7) M, the contractile response was 52% of the maximum KCl-response. The ET-1 induced contraction at 10(-7) M was inhibited by 74% after addition of the ETA-antagonist BQ-123 (10(-6) M), and by 58% by the ETB-antagonist BQ-788 (10(-6) M). Both BQ-123 and BQ-788 almost completely abolished the response to ET (10(-7) M). The selective ETB-agonist IRL-1620 also elicited vasoconstriction in the placental artery with a half maximal response at 8 x 10(-7) M. On a molar basis at 10(-7) M, the contraction by IRL-1620 as compared to ET was 30-fold lower. The contractile response of IRL-1620 (10(-6) M) was inhibited by 99% by BQ-788 (10(-6) M). After pre-contraction of the placental arteries with ET-1 (10(-7) M), the vessels relaxed in response to the nitric oxide donor, nitroglycerin (10(-6) M). The present results show that ET-1 contracts placental arteries through both ETA- and ETB-receptor activation. Nitric oxide (10(-6) M) was able to relax more than half of the initial ET-1 contraction, indicating that nitric oxide may be an important vasodilator in the placenta.