L-arginine metabolism in immune-mediated glomerulonephritis in the rat

Low-protein diets slow the progression of some renal diseases, We recently found that dietary restriction of L-arginine markedly ameliorates disease in antithymocyte serum-induced glomerulonephritis in the rat, suggesting that L-arginine may play a key role in the beneficial effects of low-protein diets, L-arginine is metabolized by nitric oxide synthases to nitric oxide and L-citrulline or by arginase to urea and L-ornithine, L-ornithine is a precursor for polyamines, which are required for cell proliferation and for proline, an essential component of collagen, in a time course of disease, we found that inducible nitric oxide synthase gene expression and nitric oxide production were increased very early, Arginase activity was significantly increased until 5 days of disease, Ornithine decarboxylase, the rate-limiting step for polyamine synthesis, was increased at 3 days coincident with the onset of cell proliferation, Gene expression of ornithine aminotransferase, a proline synthetic enzyme, was increased from day 1, paralleling increased collagen synthesis. Thus, the three pathways of L-arginine metabolism are upregulated in a manner consistent with their possible roles in the cell lysis, cell proliferation, and collagen deposition, which characterize this model of glomerulonephritis. (C) 1996 by the National Kidney Foundation, Inc.