Fetal Placental Vascular Responses to Corticotropin-Releasing Hormone in Vitro. Effects of Variation in Oxygen Tension

• Published in: Placenta (Eastbourne) 2000-09, Vol.21 (7), p.711-717
• Main Authors: Donoghue, J.F., Leitch, I.M., Boura, A.L.A., Walters, W.A.W., Giles, W.B., Smith, R., Read, M.A.
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; Blood vessels and receptors; Corticotropin-Releasing Hormone - pharmacology; Dinoprost - pharmacology; Enzyme Inhibitors - pharmacology; Female; Fetus - blood supply; Fundamental and applied biological sciences. Psychology; Humans; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide Synthase - antagonists & inhibitors; Oxygen - administration & dosage; Placenta - blood supply; Pregnancy; Regression Analysis; Vasoconstriction - drug effects; Vasodilation - drug effects; Vertebrates: cardiovascular system
• ISSN: 0143-4004; 1532-3102
• DOI: 10.1053/plac.2000.0548

In this study, using the human placenta perfused in vitro with Krebs' bicarbonate solution, we have examined the effects of changes in oxygen tension on the vasoreactivity of fetal placental blood vessels to corticotropin releasing hormone (CRH). Vasodilatory responses to human synthetic CRH were measured during sub-maximal vasoconstriction of the fetal placental circulation with prostaglandin F2α(PGF2α) (1–100μm). Decreases in fetal placental arterial perfusion pressure (FAP) were obtained with CRH under conditions of high oxygen or low oxygen tension, ≥450mmHg and ≤50mmHg, respectively. Secretion of CRH into the maternal and fetal placental circulations was measured during changes in oxygen tension in normal placentae and placentae from abnormal pregnancies complicated by pre-eclampsia. The change from high to low oxygen perfusion resulted in a small increase in the basal perfusion pressure (21±3.6 to 28.3±2.6mmHg; (P≤ 0.001, Student's paired t -test). During high oxygen perfusion, CRH (0.3–3000p m) caused a concentrationdependent reduction of the PGF2αinduced increase in FAP. However, during low oxygen perfusion, the vasodilatory effects of CRH were completely inhibited (P≤ 0.05, regression analysis, ANOVA). The effect of the NO synthase inhibitor l -nitro-ω-arginine methyl ester (l -NAME, 1–100μm), on basal FAP during high and low oxygen conditions was also established. Low oxygen perfusion significantly attenuated l -NAME-induced increases in perfusion pressure (P≤ 0.05, regression analysis, ANOVA). Low oxygen perfusion was associated with an increase in CRH secretion into the maternal but not fetal circulation. CRH release into either the maternal or fetal circulations of abnormal placentae were not significantly different from normal controls In conclusion CRH-induced vasodilatation of the fetal placental vasculature in vitro is inhibited during low oxygen perfusion. This effect may be related to reduced NO production. Reduced CRH induced vasodilation is associated with increased secretion of the CRH into the maternal but not fetal circulation.