Expression of endothelial and inducible nitric oxide synthase in human glomerulonephritis

Abstract

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 isoform involved in the local production of NO has not been identified in the human diseased kidney. We examined the expression of three isoforms of NOS, inducible NOS (iNOS), endothelial NOS (eNOS) and brain NOS (bNOS) 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 immunostained 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 vessels in the control and diseased kidneys. iNOS was localized in mesangial cells, glomerular epithelial cells and infiltrating cells in the diseased glomeruli, whereas immunostaining for iNOS was hardly detected in control kidneys. In addition, the expression pattern of eNOS in each glomerulus was the reverse of that of iNOS. In IgAN and LN, the extent of staining for eNOS correlated negatively with the degree of glomerular injury, while the extent of staining for iNOS correlated positively with the degree of glomerular injury in the same tissues. bNOS was not detected in normal or nephritic glomeruli. Our results indicate the presence of a NO pathway in human diseased kidney, and suggest that 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 important role in different way in human inflamed glomeruli.

Effects of Losartan, Tempol, and Their Combination On Renal Nitric Oxide Synthases in the Animal Model of Chronic Kidney Disease

“…In addition, in SHADR+T+L group proteinuria was lower compared to the SHADR group, but still signifi cantly higher than in the control group, and followed by a signifi cant decline of GFR. Similar fi ndings were obtained by Furusu et al who showed that the degree of glomerular injury negatively correlated with eNOS and positively with iNOS expression in proliferative glomerulonephritis [4]. Nonetheless, Ozen et al suggested that increased production of nitrite by iNOS might be responsible for proteinuria in ADR-induced nephropathy in Wistar rats [35].…”

“…In the kidney, NO is implicated in the regulation of glomerular capillary pressure, glomerular fi ltration and renal blood fl ow [2,3]. All three isoforms of NOS, endothelial NOS (eNOS), neuronal NOS (nNOS) and inducible NOS (iNOS), have been identifi ed in the kidney [4,5]. The constitutive forms of NOS, eNOS and nNOS, produce small quantities of NO, which is important for the regulation of glomerular microcirculation and the inhibition of platelet aggregation and adhesion, whereas iNOS, which can be induced by various cytokines and endotoxins, produces large quantities of NO with cytotoxic effects [2].…”

Expression of Inducible and Endothelial Nitric Oxide Synthases, Formation of Peroxynitrite and Reactive Oxygen Species in Human Chronic Renal Transplant Failure

“…In our study, immunostaining with anti-CD68 identified the majority of infiltrating cells as macrophages, suggesting that iNOS was mainly expressed by macrophages. Increments in iNOS expression have been reported in a variety of renal diseases, including IgA nephropathy and lupus nephritis (21). This suggests that iNOS upregulation is related to an inflammatory state.…”

Src Activation of NF-κB Augments IL-1β–Induced Nitric Oxide Production in Mesangial Cells

“…NO that is produced by these cells leads to activation or silencing of genes that encode antioxidant defense enzymes, matrix-metabolizing enzymes, proinflammatory mediators, and signaling mechanisms (1). In human glomerulonephritis, inducible nitric oxide synthase (iNOS) gene expression has been described in glomerular mesangial cells, as well as in local and infiltrating macrophages (2,3). Mesangial cells contribute prominently to the pathogenesis of glomerulonephritis, in part by producing a variety of cytokines and NO via iNOS, and there is evidence for participation of iNOS-generated NO in the induction, progression, or protection of several types of experimental and human glomerulonephritis.…”