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

• Published in: General pharmacology 2000-05, Vol.34 (5), p.295-301
• Main Authors: Gallardo, Victoria, Cruz, M.Antonieta, Miguel, Patricia, Carrasco, Gonzalo, González, Clemente
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Blood vessels and receptors; Endothelin Receptor Antagonists; Endothelin-1; Endothelin-1 - physiology; ET A and ET B receptors; Female; Full-term pregnancy; Fundamental and applied biological sciences. Psychology; Gestational Age; Hormone metabolism and regulation; Human placental vein; Humans; Indomethacin - pharmacology; Infant, Newborn; Infant, Premature; Maternal Age; Placenta - blood supply; Placenta - drug effects; Pregnancy; Pregnancy Trimester, Third - blood; Pregnancy. Parturition. Lactation; Preterm pregnancy; Receptor, Endothelin A; Uterine Contraction - physiology; Vasoconstriction - physiology; Vasodilator Agents - pharmacology; Veins - drug effects; Vertebrates: cardiovascular system; Vertebrates: reproduction
• ISSN: 0306-3623; 1879-0011
• DOI: 10.1016/S0306-3623(00)00070-7

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 EC 50 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 EC 50 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.