GENDER DIFFERENCES IN THE EFFECTS OF ANTENATAL BETAMETHASOME EXPOSURE ON RENAL FUNCTION IN ADULT SHEEP

Abstract

Exposure to clinically relevant doses of glucocorticoids during fetal life increases blood pressure in adult male and female sheep. The purpose of this study was to evaluate the effect of prenatal exposure to betamethasone at 80‐81 days of gestation on renal function in 17 ewes and 19 rams at 1.5 years of age. Basal glomerular filtration rate (GFR) and renal plasma flow (RPF), determined as clearance of inulin and p‐aminohppuric acid respectively were performed. An acute sodium load was administrated by a continuous infusion of hypertonic NaCl (0.0275 mEq/Kg/min) for 60 minutes. In males, basal GFR was decreased in betamethasone exposed group (B) (1.935 ± 0.08 ml/min/kg) compared with the vehicle (V) (2.267 ± 0.10 ml/min/kg) (P=0.028). In females, basal GFR was similar in both groups (1.832 ± 0.11 vs 2.133 ± 0.18 ml/min/kg). RPF was similar in B and V males (13.561 ± 0.88 vs 15.483 ± 0.40 ml/min/kg) and females (14.585 ± 0.92 in B vs 14.378 ± 1.20 ml/min/kg in V). Although basal urinary sodium excretion was similar, male B group excreted less of an acute sodium load (37.07 ± 4.4% of the dose of Na) compared with V group (53.65 ± 9.7%) (P=0.03). In contrast, prenatal betamethasone exposure in females had no effect on basal Na excretion or the percent of the Na dose excreted (98.08 ± 15.0% in B vs 92.22 ± 8.9% in V). GFR and RPF did not significantly change during the experiments. These data suggest that prenatal exposure to glucocorticoids alters renal function in adult male sheep but not in females by decreasing GFR and reducing excretion of an acute sodium load. The gender difference in the renal effects of prenatal steroid exposure suggests different mechanisms are involved in the antenatal steroid‐induced elevation in blood pressure in males and females.