EXPRESSION OF ENDOTHELIAL AND INDUCIBLE NITRIC-OXIDE SYNTHASE IN HUMAN GLOMERULONEPHRITIS

The presence of nitric oxide (NO) in the kidney has been implicated in the pathogenesis of human glomerulonephritis. However, the exact type of glomerular cells that express NO synthase (NOS) and the NOS isofor m involved in the local production of NO has not been identified in th e human diseased kidney. We examined the expression of three isoforms of NOS, inducible NOS (iNOS), endothelial NOS (eNOS) and brain NOS (bN OS) in the renal tissue of patients with IgA nephropathy (IgAN, N = 10 ), lupus nephritis (LN, N = 5), membranous nephropathy (MN, N = 5) and minimal change nephrotic syndrome (MCNS, N = 5). Sections were immuno stained and the correlation between the expression of each NOS and the degree of glomerular injury in that section was also examined. Normal portions of surgically resected kidneys served as controls. eNOS was present in glomerular endothelial cells and endothelium of cortical ve ssels in the control and diseased kidneys. iNOS was localized in mesan gial cells, glomerular epithelial cells and infiltrating cells in the diseased glomeruli, whereas immunostaining for iNOS was hardly detecte d in control kidneys. In addition, the expression pattern of eNOS in e ach glomerulus was the reverse of that of iNOS. In IgAN and LN, the ex tent of staining for eNOS correlated negatively with the degree of glo merular injury, while the extent of staining for iNOS correlated posit ively with the degree of glomerular injury in the same tissues, bNOS w as not detected in normal or nephritic glomeruli. Our results indicate the presence of a NO pathway in human diseased kidney, and suggest th at NO derived from eNOS and iNOS may be involved in the progression of renal diseases and that NO derived from each NOS may play an importan t role in different way in human inflamed glomeruli.