Thromboxane and isoprostane share the same prostanoid receptors to increase human placental tone.
As the placenta is devoid of autonomic innervation, umbilical-placental vascular tone should be under the control of tissue and humoral factors. Among the numerous stimuli capable of challenging the placental circulation, we propose that prostanoids could be responsible for the regulation of placental vascular tone. Consequently, we measured vasomotor responses to the thromboxane A(2) (TXA(2)) mimetic U-46619 and the isoprostane 8-iso-prostaglandin E(2) (8-isoPGE(2)) in the human placental vasculature. Placental tissues were collected from normotensive women after elective caesarean delivery. Cotyledons were set up in a perfusion system, whereas chorionic arteries were prepared as rings and installed in glass-jacketed tissue baths. The effects of U-46619 and 8-isoPGE(2) were measured in the absence and presence of blockers of TXA(2) receptors (TP), SQ29,548 and ICI192,605, and of PGE(2) receptors (EP), AH6809. The influence of nitric oxide (NO) was assessed with NG-nitro-L-arginine methyl ester (L-NAME). U-46619 and 8-isoPGE(2) markedly increased perfusion pressure in cotyledons and tension in chorionic arteries. Dose-response curves to both prostanoids were competitively shifted to the right by all antagonists, but to different extents. L-NAME had no significant impact on the dose-response curves to U-46619. The effects of U-46619 and 8-isoPGE(2) were found to be mediated by both TP and EP. The presence of these receptors and the actions exerted by their agonists support our postulate that prostanoids play an important regulatory role in placental vascular tone and resistance. NO, however, does not seem to be involved.
Centre de recherche, CHU Sainte-Justine, 3175, chemin de la Côte Ste-Catherine, Montréal, Québec H3T 1C5, Canada.
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Hausermann
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J
St-Louis
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000328:Adult; D019086:Bridged Bicyclo Compounds, Heterocyclic; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated; D005260:Female; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology; D066298:In Vitro Techniques; D028421:Isoprostanes / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D010477:Perfusion; D010920:Placenta / Q000098:blood supply* / Q000187:drug effects; D011247:Pregnancy; D011453:Prostaglandins / Q000494:pharmacology*; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors / Q000502:physiology*; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D013931:Thromboxanes / Q000494:pharmacology*; D044004:Xanthones / Q000494:pharmacology
D019086:Bridged Bicyclo Compounds, Heterocyclic; D004146:Dioxanes; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D028421:Isoprostanes; D011453:Prostaglandins; D018078:Receptors, Prostaglandin E; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D013931:Thromboxanes; D044004:Xanthones; C057498:ICI 192605; D009569:Nitric Oxide; C053876:6-isopropoxy-9-oxoxanthene-2-carboxylic acid; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C045749:SQ 29548; D015232:Dinoprostone; D019331:NG-Nitroarginine Methyl Ester; C011987:8-isoprostaglandin E2