Urinary excretion of nitrite and nitrate in experimental glomerulonephritis reflects systemic immune activation and not glomerular synthesis

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Abstract
In immune-induced glomerulonephritis (gn), glomeruli (gl) synthesize nitric oxide (NO), and urinary nitrite (NO2−) excretion is increased. In mammals on a low nitrate (NO3−) diet, urinary NO3− is a measure of endogenous NO3− synthesis. Excretion is increased after administration of macrophage activators, reflecting induction of NO production. To determine whether increased urinary NO2− gn is due to glomerular synthesis we studied urinary NO2−/NO3− in accelerated nephrotoxic nephritis induced by preimmunization with rabbit immunoglobulin G (IgG), followed by rabbit anti-rat nephrotoxic globulin, and in control rats similarly preimmunized with rabbit IgG, but followed by normal rabbit serum. Both urinary NO2− and NO3− were increased by i.p. preimmunization with rabbit IgG (peak 463 ± 171 nmol NO2−/60.3 ± 9.4 nmol NO3/24 h, P2− and NO3− compared with preimmunization levels). Repeat immunization with i.v. rabbit anti-rat nephrotoxic globulin (nephritic rats) or normal rabbit globulin (control rats) again increased urinary NO2− and NO3−. There was no statistically significant difference in urinary NO2 and NO3− levels between nephritic rats where globulin had nephrotoxic activity and the control rats injected with normal rabbit globulin, despite increased NO2−synthesis in ex vivo nephritic glomeruli after nephrotoxic globulin (7.9 ± 1.9 nmol/2000 gl/48 h; controls 3.2 ± 1.0 nmol/2000 gl/48 h). Thus neither urinary NO2− nor NO3− levels reflect local activation of the NO pathway in glomeruli. As reported for other stimulants, we show here that systemic stimulation with foreign antigen increased NO synthesis.