Short-term effects of glucocorticoids in the human fetal-placental circulation in vitro.
A number of studies demonstrate that both long-term and short-term exposure to glucocorticoids alters vascular function. We have examined whether the short-term administration of glucocorticoids into the human fetal-placental circulation affects placental arterial pressure and alters vascular responses to vasoconstrictive and vasodilator agents. Single lobules of term human placentae were bilaterally perfused in vitro with Krebs' solution (maternal and fetal, 5 ml/min Krebs, 95% O2, 5% CO2, 37 C, pH 7.3), and changes in fetal-placental arterial perfusion pressure were measured. Dexamethasone (100 nM) infusion for 1 h into the fetal-placental circulation caused a significant decrease in basal arterial pressure (n = 19, t test, P < 0.05). Continuous dexamethasone infusion (100 nM) did not alter vasoconstrictive responses to PGF(2alpha) (0.5-120 pM, n = 12, ANOVA, P > 0.05) or potassium chloride (5-600 mM, n = 12, ANOVA, P > 0.05) or vasodilator responses to CRH (53-7400 pM, n = 13, ANOVA, P > 0.05). However when fetal-placental vessels were submaximally preconstricted and then infused with dexamethasone alone (40 nM-10 microM), there was a dose-dependent decrease in arterial pressure (n = 8). Dexamethasone-induced dilation was not inhibited by blocking nitric oxide synthase or cyclo-oxygenase activity. These data suggest that dexamethasone can cause dilation in the fetal-placental circulation, possibly via an endothelium-independent pathway.
Clifton
Vicki L
VL
Mothers and Babies Research Centre, Department of Endocrinology, John Hunter Hospital, Hunter Region Mail Center, Newcastle, New South Wales 2310, Australia.
Wallace
Euan M
EM
Smith
Roger
R
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005333:Fetus / Q000098:blood supply*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D021041:Placental Circulation / Q000187:drug effects*; D011189:Potassium Chloride / Q000494:pharmacology; D011247:Pregnancy; D012039:Regional Blood Flow / Q000187:drug effects; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D019335:Nitroarginine; D011189:Potassium Chloride; D003907:Dexamethasone; D003346:Corticotropin-Releasing Hormone; D019001:Nitric Oxide Synthase