Chronic UUO in the neonatal rat impairs renal growth and development, and activates the intrarenal renin-angiotensin system. To elucidate the role of AII and its receptors (AT1 and AT2) in mediating the renal cellular response to UUO, Sprague-Dawley rats were subjected to UUO within the first 48 h of life, and kidneys were removed 72 h later for determination of cellular proliferation by PCNA labeling and apoptosis by the TUNEL technique. Rats were divided into 6 groups (n = 4-8 each group), and received either vehicle (V); AII (3.6 μg/d); AT1 receptor inhibitor, losartan (L, 40 mg/kg/d); AT2 receptor inhibitor, PD123319, (PD, 70 μg/d); AII+L; or AII+PD. The relative density of PCNA- and TUNEL-positive renal tubular epithelial cells was determined for each group. Shown in the table is the mean number of labeled cells/field ± SEM for the obstructed kidney. AII increased cellular proliferation in the obstructed kidney, an effect that was blocked by L but not PD (p<0.05 by 2 way ANOVA). AII also increased the number of apoptotic tubular cells in the obstructed kidney, an effect that was blocked by either L or PD (p<0.05 by 2 way ANOVA). Compared to the obstructed kidney, the number of PCNA-positive cells was increased, and that of TUNEL-positive cells was decreased in the intact opposite kidney (not shown) (p<0.05). We conclude that UUO in the neonatal rat decreases cellular proliferation and increases apoptosis in the obstructed kidney. Endogenous AII contributes to maintenance of cell proliferation in the obstructed kidney through stimulation of AT1 receptors, an effect that can be enhanced by exogenous AII. However, AII also contributes to apoptosis through stimulation of AT1 and AT2 receptors. Elucidation of the role of AII in the renal response to UUO may lead to new approaches to the mangement of congenital obstructive nephropathy.

Table 1
Full size table