Mechanisms of endothelin-1-induced contraction in isolated placental veins from normal full-term and preterm pregnancies

Abstract

This study characterizes the reactivity of human chorionic plate vein in full-term (39.4±0.3 weeks of gestation) and preterm (34.4±0.6 weeks of gestation) pregnancy to endothelin-1 (ET-1) and attempts to characterize ET-1 receptor subtype, and the contribution of nitric oxide and cyclooxygenase products in these responses. In placental veins from full-term and preterm pregnant women, cumulative addition of ET-1 (10⁻¹⁰–10⁻⁶ M) caused marked and long-lasting concentration-dependent contractile responses. The mean EC₅₀ and E_max values for ET-1-induced venoconstriction did not differ between the full-term and preterm pregnancy groups. In the veins from preterm placental preparations, the ET_A receptor-selective antagonist cyclo(d-α-aspartyl-l-propyl-d-valyl-l-leucyl-d-tryptophyl (BQ123) reduced the ET-1-induced contraction by 28.6±2.4%, compared to a decline in tension of 51.2±4.2% in the full-term placental vessels. The ET_B receptor-selective antagonist, N-[N-[N-[2,6-dimethyl-1piperidinyl)carbonyl]-4-methyl-l-leucyl]-1-(methoxycarbonyl)-d-tryptophyl]-d-norleucinemonosodium (BQ788), did not influence ET-1-induced contraction in placental vein from both pregnancy groups in terms of maximal contraction and sensitivity. Pretreatment with the cyclooxygenase inhibitor, indomethacin (1 μM) and the nitric oxide synthase inhibitor N^w-nitro-l-arginine (NOLA, 100 μM) did not significantly affect either the EC₅₀ or the maximum contraction to ET-1 in veins from normal full-term and preterm preparations. The results of this study suggest that there is no correlation between ET-1-induced vasoconstriction and gestational age and that this vasoconstriction is mediated predominantly via ET_A receptor subtype in both groups of pregnant women, independent of NO and eicosanoids.