Effect of prenatal Betamethasone (B) exposure on sodium excretion in response to intrarenal infusions of Angiotensin II (Ang II) and its antagonist in male sheep.

Prenatal exposure to clinically relevant doses of Betamethasone (B) reduces nephron number in adult sheep, but its effects on renal function are unknown. Therefore, we evaluated if prenatal B exposure alters sodium excretion (UNa) in response to intrarenal infusions (IRI) of angiotensin II (AII) with or without its antagonists (Candesartan (C) [type 1] and PD123319 (PD) [type 2] receptor blockers) in adult male sheep. 1.5 year old male sheep which were exposed to B (n=6) or vehicle (V, n=6) at 80‐81 days gestation and born at term received renal arterial infusions of AII (1ng/kg/min) with or without antagonists for 24 hours. Na excretion (UNa) was measured during the infusions. Analysis of variance (ANOVA) and T‐test were used for data analysis. AII infusion decreased UNa from 0.39±0.07 to 0.14±0.04mM/hr/Kg (p<0.01) in B sheep, and from 0.37±0.06 to 0.18±0.05 in V sheep. AII plus PD decreased UNa in V sheep but not in B sheep (decreases were ‐0.27±0.09 in V sheep and ‐0.09 ±0.04mM/hr/Kg in B sheep, p=0.059). In presence of C, UNa initially decreased in both groups (from 0.39±0.09 to 0.13±0.03 in V and from 0.26±0.07 to 0.12±0.03mM/hr/Kg in B sheep), and then increased. The increase was 0.39± 0.09 in vehicle sheep and 0.25±0.05 in B (p=0.05). The data suggest that the natriuretic response to stimulation of the AII type 2 receptor is converted to an antinatriuresis by prenatal B exposure. Supported by NIH grants HD 047584 and HD17644