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

Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria 3010, Australia

Address all correspondence and requests for reprints to: Dr. Karen Moritz, Howard Florey Institute, University of Melbourne, Parkville, 3010, Australia. E-mail: k.moritz{at}hfi.unimelb.edu.au.

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.

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