Previously, we showed that neonatal induced chronic partial unilateral ureteral obstruction (PUUO) of the multipapillary pig kidney decreased glomerular filtration rate (GFR) of the obstructed kidney. We hypothesized that ANG II and nitric oxide (NO) are important for the changes in renal function and in the present study we examined the effects of chronic AT1 receptor blockade using CV-11974 (0.12 mg/h candesartan from age 23 to 30 days) on kidney function development after PUUO was induced in 2-day-old piglets. Moreover, the effect of superimposed acute NO inhibition using N G -nitro-L-arginine methyl ester (L-NAME; 15 mg/kg) was examined to identify if this has diagnostic potential. PUUO significantly increased GFR in the nonobstructed contralateral kidney independent of candesartan. In candesartan-treated piglets, the L-NAME-induced GFR reduction seen in normal and nonobstructed kidneys was absent in the partial obstructed kidneys. Urine output and fractional excretion of water were increased from the partial obstructed kidneys. Consistent with this immunohistochemical analyses showed a reduced aquaporin-2 labeling in the collecting duct principal cells. Moreover, renal sodium handling was compromised by PUUO evidenced by an increased fractional excretion of sodium which was enhanced by candesartan treatment. In conclusion, our findings suggest that the counterbalance between AT1 receptor-mediated vasoconstriction and NO-mediated vasodilatation which maintain GFR in normal young porcine kidneys is changed by neonatal induced chronic PUUO. This may have diagnostic potential in children with suspected congenital obstruction. Our results also demonstrate compromised tubular functions in response to chronic PUUO despite preservation of glomerular function.hydronephrosis; stereology; glomerular filtration rate; aquaporin 2 PRENATAL DIAGNOSED UNILATERAL hydronephrosis persisting postnatal may be caused by partial obstruction at the ureteropelvic junction and hydronephrosis is found in ϳ0.5% of newborns potentially leading to obstructive nephropathy (36). Major challenges exist in the clinical management of the infant with congenital obstructive nephropathy. Renal function of the hydronephrotic kidney is often preserved despite severe dilatation (13). Measuring kidney function may therefore not disclose obstruction-induced impairment at the cellular and molecular levels including the activation of vasoconstrictors and cytokines that has been documented in animal models (6). Thus, for infants with unilateral hydronephrosis, there is a need to predict which patients are candidates for pyeloplasty and to estimate the acceptable duration of observation before proceeding to surgical intervention (13).In recent studies, we demonstrated that neonatal induced partial unilateral ureteral obstruction (PUUO) in piglets decreases glomerular filtration rate (GFR) and causes a significant reduction in the number of nephrons (11,12,14). However, the regulation of these pathophysiological changes has not been addressed in the neon...

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