Role of nitric oxide in renal tubular apoptosis of unilateral ureteral obstruction

Background. The obstructed kidney in unilateral ureteral obstruction (UUO) is characterized by renal atrophy and tissue loss, which is mediated by ren al tubular apoptosis. We sought to determine whether NO is involved in rena l tubular apoptosis in vitro and in vivo. Methods. Rat renal tubular epithetial cells (NRK-52E) were subjected to mec hanical stretch, and apoptosis and cell size were analyzed by flow cytometr y. Furthermore, we studied UUO in mice lacking the gene for inducible nitri c oxide synthase (iNOS-/-) and their wild-type littermates. Tubular apoptos is and proliferation were detected by immunostaining. NOS activity and NOS expression were assessed by a citrulline assay and Western blot, respective ly. Results. Stretching-induced apoptosis in NRK-52E, which was reduced when NO was increased; conversely, stretch-induced apoptosis was increased when a NOS inhibitor was added to the cells. Stretched cells are larger and more a poptotic than unstretched cells. In UUO, the obstructed kidney of iNOS -/-m ice exhibited more apoptotic renal tubules than the wildtype mice through 1 4 days of UUO. The obstructed kidney of iNOS-/- mice at day 3 showed more p roliferative tubules compared with wild type. The obstructed kidney of wild -type mice exhibited higher total NOS activity until day 7 after UUO compar ed with iNOS-/- mice. However, the obstructed kidney of day 14 wild-type mi ce exhibited significantly lower iNOS activity and protein compared with th e day 0 kidney. Conclusion. These results suggest that mechanical stretch is related to ren al tubular apoptosis and that NO plays a protective role in this system in UUO.