Mechanisms of endothelin-1-induced contraction in isolated placental veins from normal full-term and preterm pregnancies.
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-alpha-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 microM) and the nitric oxide synthase inhibitor N(w)-nitro-L-arginine (NOLA, 100 microM) 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.
Gallardo
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Departamento de Fisiología, Facultad de Ciencias Biológicas, Universidad de Concepción, Casilla 160-C, Concepción, Chile. clgonzal@udec.al
Cruz
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MA
Miguel
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P
Carrasco
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González
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C
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000502:physiology*; D005260:Female; D005865:Gestational Age; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007231:Infant, Newborn; D007234:Infant, Premature; D008423:Maternal Age; D010920:Placenta / Q000098:blood supply* / Q000187:drug effects; D011247:Pregnancy; D011263:Pregnancy Trimester, Third / Q000097:blood; D044022:Receptor, Endothelin A; D014590:Uterine Contraction / Q000502:physiology*; D014661:Vasoconstriction / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*; D014680:Veins / Q000187:drug effects
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D044022:Receptor, Endothelin A; D014665:Vasodilator Agents; D007213:Indomethacin