We have shown that the administration of Ang II AT1 receptor antagonist (ARA) during nephrogenic period reduces nephron number similarly in males and females. However, renal structural and functional associated changes are greater in males. Our objective was to examine whether the renal ability to respond to vasodilatory and natriuretic stimuli are affected in rats with a reduced nephron number, and whether this possible alteration is gender and/or aging-dependent. Newborn SD rats were treated with vehicle or an ARA (7 mg/Kg/day) during the first 14 postnatal days. Renal function was examined in anesthetized rats in response to an aminoacids infusion and to an acute volume expansion (VE).

Aminoacids infusion at 3 months of age elicited an increase (P<0.05) of glomerular filtration rate (1.47 ± 0.12 to 1.91 ± 0.11 ml/min/gr) renal plasma flow (4.3 ± 0.2 to 5.4 ± 0.2 ml/min/gr), natriuresis and diuresis in vehicle-treated males. Renal vasodilatation and excretory response to aminoacids were abolished in ARA-treated rats. VE-induced natriuresis and diuresis were reduced (P<0.05) by more than 38% in ARA-treated males and females at 3 months, but only aggravated in ARA-treated males at 9 months of age with a further reduction (33%, P<0.05) of the renal excretory ability. Our results demonstrate that the vasodilatory and excretory responses to an increase in aminoacids and the renal excretory ability to eliminate a VE are impaired in males and females when nephron number is reduced during nephrogenic period. Renal excretory ability is only aggravated by aging in males.