Reduced nitric oxide synthase activity in rats with chronic renal disease due to glomerulonephritis

L. Wágner, Amy Riggleman, Aaron Erdely, William Couser, Chris Baylis

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Abstract

Background. Animal studies with systemic nitric oxide synthase (NOS) inhibition and renal ablation, suggest that NO deficiency is both a cause and a consequence of chronic renal disease (CRD). Methods. This study examined a glomerulonephritis (GN) model of CRD to determine if NO is deficient. In addition to measuring indices of renal function (proteinuria, creatinine clearance, structural damage), indices of total and renal nitric oxide production also were assessed (total NOX excretion, renal NOS activity, renal NOS protein abundance, plasma levels of NOS substrate and endogenous inhibitor). Results. Rats developed increasing proteinuria 12 to 20 weeks after induction of GN (with anti-glomerular basement membrane, GBM, antibody) and at 20 weeks exhibited reduced creatinine clearances and increased glomerulosclerosis relative to age-matched controls. Total NOX excretion was reduced and the renal cortical NOS activity and neuronal NOS (nNOS) abundance was decreased relative to controls. There was no impact on renal or aortic endothelial NOS expression or cerebellar nNOS. The plasma L-arginine (Arg) concentration was well maintained but plasma asymmetric dimethylarginine (ADMA) concentration increased in GN versus control animals. Conclusions. Total and renal NOS activity is reduced in the GN model of CRD due to increased circulating endogenous NOS inhibitors and decreased renal nNOS abundance.

Original languageEnglish
Pages (from-to)532-536
Number of pages5
JournalKidney International
Volume62
Issue number2
DOIs
Publication statusPublished - 2002

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Keywords

  • Arginine
  • Asymetric dimethylarginine
  • Endothelial NOS
  • ESRD
  • Neuronal NOS
  • Nitrate + nitrite
  • Nitric oxide
  • Progressive renal disease

ASJC Scopus subject areas

  • Nephrology

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