Fetal renal and blood pressure responses to steroid infusion after early prenatal treatment with dexamethasone.
Maternal infusion of dexamethasone for 48 h early in gestation results in upregulation of mRNA for mineralocorticoid and glucocorticoid (MR and GR) receptors and angiotensin II receptors in ovine fetal kidneys late in gestation. This study sought to determine whether dexamethasone exposure results in changes in renal function and blood pressure responsiveness to infused cortisol or aldosterone in the late-gestation fetus. Merino ewes carrying single fetuses were infused with isotonic saline (Sal; n = 9) or dexamethasone (Dex, 0.48 mg/h; n = 10) for 48 h between days 26 and 28 of gestation (term = 150 days). At 115-122 days, renal function and blood pressure were measured in fetuses during a 4-h infusion of saline, cortisol (100 microg/h), or aldosterone (5 microg/h). Infusions were given in random order at least 2 days apart. Basal blood pressure and renal function were similar in Sal and Dex groups and did not change over the course of saline infusion. Cortisol infusion caused similar increases in blood pressure, urine flow, and glomerular filtration rate (GFR) in the groups. Aldosterone infusion caused a significantly different GFR response between the groups [P(treatment x time) < 0.05], but increase in K excretion and decrease in Na-to-K ratio were similar in the groups. The similar results obtained with cortisol and aldosterone infusion suggest no increased renal functional maturity to those hormones after early prenatal dexamethasone exposure. This suggests that changes in mRNA for MR and GR in kidneys of dexamethasone-exposed fetuses do not result in functional differences and highlights the renin-angiotensin system, as reported previously, as more important in this model.
Moritz
Karen M
KM
Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Australia. karen.moritz@med.monash.edu.au
Jefferies
Andrew
A
Wintour
E Marelyn
EM
Dodic
Miodrag
M
D000450:Aldosterone / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000502:physiology; D005865:Gestational Age; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006854:Hydrocortisone / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000196:embryology; D011188:Potassium / Q000652:urine; D011247:Pregnancy; D012756:Sheep; D012964:Sodium / Q000652:urine
D005938:Glucocorticoids; D000450:Aldosterone; D003907:Dexamethasone; D012964:Sodium; D011188:Potassium; D006854:Hydrocortisone