Inducible nitric oxide synthase modulates hydronephrosis following partial or complete unilateral ureteral obstruction in the neonatal mouse

Yoo KH, Thornhill BA, Forbes MS, Chevalier RL. Inducible nitric oxide synthase modulates hydronephrosis following partial or complete unilateral ureteral obstruction in the neonatal mouse. Am J Physiol Renal Physiol 298: F62-F71, 2010. First published November 4, 2009; doi:10.1152/ajprenal.00234.2009.-To investigate the role of endogenous inducible nitric oxide synthase (iNOS) in the response of the developing kidney to unilateral ureteral obstruction (UUO), neonatal iNOS null mutant (-/-) and wild-type (WT) mice were subjected to partial or complete UUO. At 7 and 21 days of age, apoptosis, renin, vascular endothelial growth factor (VEGF), fibroblasts (antifibroblast-specific peptide 1), myofibroblasts (alpha-smooth muscle actin), macrophages (F4/80), and collagen were measured in kidney tissue. Compared with WT, renal parenchymal thickness was increased, with preservation of the papilla, in -/- mice with partial UUO, but decreased in -/- mice with complete UUO. Ureteral peristalsis increased with severity of pelvic dilatation in WT, and increased further in -/- mice with partial UUO. Apoptosis, fibroblasts, and macrophages were increased in -/- mice with complete UUO, but there was no effect of iNOS on other histological parameters following complete UUO. Renin was decreased in -/- mice with partial UUO. There was no effect of iNOS genotype on renal collagen accumulation at either 7 or 21 days of age. These results are consistent with an injurious role for endogenous iNOS following partial UUO by inhibiting ureteral peristalsis and increasing renal renin although renal fibrosis is not affected. In contrast, in mice with complete UUO, iNOS attenuates apoptosis and enhances renal parenchymal thickness. Alterations in the severity of ureteral obstruction may therefore influence the effect of iNOS on long-term renal injury.