Endothelin‐induced contractions in placental arteries is mediated by both ETA‐ and ETB‐receptors

Abstract

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 °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 × 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 ET_A -antagonist BQ-123 (10⁻⁶ M), and by 58% by the ET_B -antagonist BQ-788 (10⁻⁶ M). Both BQ-123 and BQ-788 almost completely abolished the response to ET (10⁻⁷ M). The selective ET_B -agonist IRL-1620 also elicited vasoconstriction in the placental artery with a half maximal response at 8 × 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 ET_A- and ET_B-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.