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DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY

Gender differences in the effects of antenatal betamethasone exposure on renal function in adult sheep

¹Department of Obstetrics and Gynecology and Center of Research for Obstetrics and Gynecology, ²Hypertension Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina

Submitted 29 July 2008 ; accepted in final form 20 November 2008

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 effects of prenatal exposure to betamethasone at 80–81 days of gestation on renal function in ewes and rams at 1.5 yr of age. In prenatal betamethasone-exposed males, compared with the vehicle-exposed animals, basal glomerular filtration rate (GFR) (1.93 ± 0.08 vs. 2.27 ± 0.10 ml·min^–1·kg body wt^–1) and the ability to excrete an acute Na⁺ load (37.1 ± 4.4 vs. 53.7 ± 9.7%) were reduced. (P < 0.03 and P = 0.03, respectively). In contrast, prenatal betamethasone exposure had no effect on basal GFR, Na⁺ excretion, or the percentage of the Na⁺ load excreted during the experiment in females. Systemic infusions of ANG-(1–7) at 9 ng·min^–1·kg^–1 for 2 h had minimal effects on basal GFR, renal plasma flow, and Na⁺ excretion in males but increased Na⁺ excretion in females. However, the percentage of Na⁺ load excreted during ANG-(1–7) infusion did not change in prenatal betamethasone-exposed females (113.1 ± 14.2 vs. 98.1 ± 12.2%) compared with the significant increase in vehicle females (139.2 ± 22.3 vs. 92.2 ± 7.5%) (P = 0.01). The data indicate that antenatal betamethasone exposure produces gender-specific alternations in renal function and thus suggest that different mechanisms underlie the antenatal steroid-induced elevations in blood pressure in male and female offspring.

prenatal steroid exposure; sodium load; glomerular filtration rate; sodium excretion; angiotensin-(1–7)