AMINOGUANIDINE REDUCES GLOMERULAR INDUCIBLE NITRIC-OXIDE SYNTHASE (INOS) AND TRANSFORMING-GROWTH-FACTOR-BETA-1 (TGF-BETA-1) MESSENGER-RNA EXPRESSION AND DIMINISHES GLOMERULOSCLEROSIS IN NZB W F-1 MICE/

Over-expression of iNOS is implicated in the pathogenesis of glomerulo nephritis in animal models of systemic lupus erythematosus. The aim of this study was to evaluate the effect of aminoguanidine, a selective inhibitor of iNOS, for the protection from glomerulosclerosis in NZB/W F-1 mice. Female NZB/W F-1 mice (n = 8) were treated with aminoguanid ine (1 g/l) in drinking water for 4 months starting at age 2 months be fore the onset of glomerulonephritis. Controls were age- and sex-match ed mice (n = 10) without aminoguanidine treatment. By glomerular micro dissection and reverse-transcription competitive polymerase chain reac tion. we found that glomerular iNOS/beta-actin and TGF-beta 1/beta-act in mRNA ratios were reduced 15.1% (P<0.05) and 61.3% (P<0.01), respect ively, in aminoguanidine-treated mice. Aminoguanidine significantly re duced the glomerular iNOS staining, urinary nitrite production and deg ree of glomerulosclerosis. In addition, the glomerular volume and mean glomerular cell number were reduced 33.2% (P < 0.01) and 32.8% (P < 0 .01), respectively. Likewise, the urinary proteinuria was also signifi cantly reduced by aminoguanidine. These results indicate that administ ration of aminoguanidine may reduce the progression of glomerulosclero sis in NZB/W F-1 mice, possibly through inhibition of glomerular nitri c oxide production.