Maternal Glucocorticoid Treatment Programs Alterations in the Renin-Angiotensin System of the Ovine Fetal Kidney

Ovine fetuses exposed to high concentrations of synthetic (dexamethasone, D) or naturally occurring glucocorticoids (cortisol, F) in utero during early gestation develop high blood pressure in adulthood. To investigate potential mechanisms involved, we examined the role of the renal renin-angiotensi...

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Bibliographic Details
Published in:Endocrinology (Philadelphia) 2002-11, Vol.143 (11), p.4455-4463
Main Authors: Moritz, K. M, Johnson, K, Douglas-Denton, R, Wintour, E. M, Dodic, M
Format: Article
Language:English
Subjects:
Angiotensin II - administration & dosage
Angiotensinogen - genetics
Animals
Blood Pressure - drug effects
Blotting, Western
Dexamethasone - administration & dosage
Dexamethasone - adverse effects
Diuresis - drug effects
Female
Gestational Age
Glomerular Filtration Rate - drug effects
Glucocorticoids - administration & dosage
Glucocorticoids - adverse effects
Hydrocortisone - administration & dosage
Hydrocortisone - adverse effects
Hypertension - chemically induced
Immunohistochemistry
Kidney - embryology
Kidney - physiology
Maternal-Fetal Exchange
Nucleic Acid Hybridization
Organ Size - drug effects
Polymerase Chain Reaction
Pregnancy
Prenatal Exposure Delayed Effects
Receptor, Angiotensin, Type 1
Receptor, Angiotensin, Type 2
Receptors, Angiotensin - genetics
Renin-Angiotensin System - drug effects
RNA, Messenger - analysis
Sheep
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Summary:Ovine fetuses exposed to high concentrations of synthetic (dexamethasone, D) or naturally occurring glucocorticoids (cortisol, F) in utero during early gestation develop high blood pressure in adulthood. To investigate potential mechanisms involved, we examined the role of the renal renin-angiotensin system (RAS). Ewes were infused with isotonic saline (S, n = 11), D (n = 12, 0.48 mg/h), or F (n = 5, 5 mg/h) for 48 h between d 26 and 28 of gestation (term = 150 d). Ewes carrying twins (S, n = 5; D, n = 6; F, n = 5) were killed at 130 d of gestation. The mRNA levels for angiotensinogen, the AT1 receptor and AT2 receptor, were increased in the fetal kidneys after D treatment. Prenatal infusions of F produced similar effects on the AT1 receptor. Single fetuses (S, n = 6; D, n = 6) were cannulated and infused with angiotensin II for 3 d beginning at 127 d of gestation. Basal blood pressure was similar in both groups and increased similarly with angiotensin II infusion. However, increases in urine flow and glomerular filtration rate were significantly reduced and kidney weights increased in the D-treated group. These results indicate that treatment with D very early in gestation causes significant alterations in the RAS in the fetal kidney 100 d later with functional consequences. Changes in the RAS in the developing kidney may be an important mechanism in the development of adult disease.
ISSN:0013-7227
1945-7170
DOI:10.1210/en.2002-220534