Aminoguanidine reduces glomerular inducible nitric oxide synthase (iNOS) and transforming growth factor-beta 1 (TGF-beta1) mRNA expression and diminishes glomerulosclerosis in NZB/W F1 mice

Clin Exp Immunol. 1998 Aug;113(2):258-64. doi: 10.1046/j.1365-2249.1998.00632.x.


Over-expression of iNOS is implicated in the pathogenesis of glomerulonephritis 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 F1 mice. Female NZB/W F1 mice (n = 8) were treated with aminoguanidine (1 g/l) in drinking water for 4 months starting at age 2 months before the onset of glomerulonephritis. Controls were age- and sex-matched mice (n = 10) without aminoguanidine treatment. By glomerular microdissection and reverse-transcription competitive polymerase chain reaction, we found that glomerular iNOS/beta-actin and TGF-beta1/beta-actin mRNA ratios were reduced 15.1% (P<0.05) and 61.3% (P<0.01), respectively, in aminoguanidine-treated mice. Aminoguanidine significantly reduced the glomerular iNOS staining, urinary nitrite production and degree 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 significantly reduced by aminoguanidine. These results indicate that administration of aminoguanidine may reduce the progression of glomerulosclerosis in NZB/W F1 mice, possibly through inhibition of glomerular nitric oxide production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight
  • Cell Count
  • Creatine / blood
  • Creatine / urine
  • Crosses, Genetic
  • Enzyme Inhibitors / therapeutic use
  • Female
  • Guanidines / therapeutic use*
  • Hypertrophy
  • Kidney Glomerulus / pathology*
  • Lupus Nephritis / drug therapy*
  • Male
  • Mice
  • Mice, Inbred NZB
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / biosynthesis*
  • Nitric Oxide Synthase / genetics
  • Nitric Oxide Synthase Type II
  • Nitrites / urine
  • Organ Size
  • Proteinuria
  • RNA, Messenger / analysis
  • Transforming Growth Factor beta / biosynthesis*
  • Transforming Growth Factor beta / genetics


  • Enzyme Inhibitors
  • Guanidines
  • Nitrites
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Creatine
  • pimagedine