Endothelin-induced contractions in placental arteries is mediated by both ETA- and ETB-receptors.
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.
Department of Women and Child Health, Karolinska Institute and Hospital, Stockholm, Sweden.
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Ostlund
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D000328:Adult; D001158:Arteries / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000494:pharmacology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009569:Nitric Oxide / Q000502:physiology; D005996:Nitroglycerin / Q000494:pharmacology; D010920:Placenta / Q000098:blood supply*; D011247:Pregnancy; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000819:agonists / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D014665:Vasodilator Agents; D009569:Nitric Oxide; D005996:Nitroglycerin