title: The nitric oxide pathway in glomerulonephritis.
abstract: Nitric oxide has fundamental roles in the modulation of many cell functions. In glomerulonephritis, generation of nitric oxide by the acutely inflamed glomerulus has recently been confirmed, with evidence that synthesis occurs through induction of the inducible form of nitric oxide synthase. Recent studies implicate infiltrating macrophages as a major source of this activity, although intrinsic glomerular cells may contribute as nitric oxide synthase has been found in cytokine-stimulated mesangial, endothelial and epithelial cells in culture. Cytokines, which are known to have a central role in glomerulonephritis, are the most probable stimulus of nitric oxide synthase induction in vivo, although this awaits confirmation. A role for nitric oxide in the pathophysiology of glomerulonephritis is not clearly defined at present but is strongly suggested by evidence for participation of nitric oxide in other immune and inflammatory diseases. The evidence evaluated in this review emphasizes that the role is certain to be complex. As yet it is not possible to predict whether the modulatory effects of nitric oxide on glomerular haemodynamics, vascular integrity, leucocyte infiltration and intrinsic glomerular cell responses are predominantly protective or cytotoxic. There are presently only two fully published reports of inhibition of nitric oxide in models of glomerulonephritis, one of which showed an exacerbation of acute heterologous nephrotoxic injury, and the other showed amelioration of chronic autoimmune glomerulonephritis. It is therefore premature to speculate on the effects of nitric oxide inhibition in glomerulonephritis. New insights await further understanding of the regulation of the inducible form of nitric oxide synthase in glomerulonephritis and the availability of specific inhibitors of this enzyme.
authors.affiliation: Department of Histopathology, St. Mary's Hospital Medical School, London, UK.
authors.forename: V
authors.initials: V
authors.lastname: Cattell
authors.forename: T
authors.initials: T
authors.lastname: Cook
mesh_terms: D000818:Animals; D005921:Glomerulonephritis / Q000378:metabolism*; D006801:Humans; D007105:Immune Complex Diseases / Q000276:immunology / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D009569:Nitric Oxide