Elsevier

Kidney International

Volume 62, Issue 2, August 2002, Pages 532-536
Kidney International

Vascular Biology – Hemodynamics – Hypertension
Reduced nitric oxide synthase activity in rats with chronic renal disease due to glomerulonephritis

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

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.

Keywords

neuronal NOS
endothelial NOS
arginine
asymetric dimethylarginine
nitrate + nitrite
ESRD
nitric oxide
progressive renal disease

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