Lack of a role for inducible nitric oxide synthase in an experimental model of nephrotic syndrome

Puromycin aminonucleoside (PAN) administration in rats produces an experime ntal model of nephrotic syndrome characterized by glomerular epithelial cel l injury and proteinuria. The purpose of this study was to examine the role of nitric oxide (NO) in this model of minimal change glomerular disease. A minoguanidine (AG) was used to inhibit inducible nitric oxide synthase (iNO S). Sprague-Dawley rats were divided into Control (N = 9), PAN (N = 14), AG (N = 2), and PAN + AG (N = 12) treatment groups. Control animals received saline (i.v.), PAN animals received PAN (75 mg/kg, i.v.), and PAN + AG anim als received PAN plus AG (50 mg/kg, i.p., twice daily). AG animals received a saline injection (i.v.) on day 0 in the place of PAN and then AG on the same schedule as the PAN + AG group. Animals were kept in metabolic cages, and urinary protein excretion and nitrite (NO2-) excretion were measured da ily. PAN administration increased urinary NO2- excretion by day 2, and leve ls remained elevated through day 7. AG prevented this PAN-induced increase in urinary NO2- excretion. Plasma nitrate (NO3-) and NO2- (NOx) concentrati ons were also increased in the PAN and PAN + AG groups. iNOS protein expres sion was not detected in either the glomeruli or the cortex at day 7. Prote inuria developed in PAN animals on day 4 and increased steadily through day 7. PAN + AG animals shelved a pattern similar to that of the PAN group. Th ese results indicated that in contrast to models of proliferative glomerulo nephritis, NO formation during PAN-induced nephrotic syndrome is increased but does not. participate in the development of glomerular injury as measur ed by proteinuria. BIOCHEM PHARMACOL 60;1:137-143, 2000. (C) 2000 Elsevier Science Inc.