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 NO(X) 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 NO(X) 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.
Division of Exercise Physiology, Department of Physiology, West Virginia University, Morgantown,West Virginia, USA.
Laszlo
L
Wagner
Amy
A
Riggleman
Aaron
A
Erdely
William
W
Couser
Chris
C
Baylis
D000818:Animals; D000906:Antibodies; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D001323:Autoantibodies; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D005921:Glomerulonephritis / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008297:Male; D009566:Nitrates / Q000652:urine; D009569:Nitric Oxide / Q000652:urine; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D009573:Nitrites / Q000652:urine; D011507:Proteinuria / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000906:Antibodies; D001323:Autoantibodies; D009566:Nitrates; D009573:Nitrites; C051951:antiglomerular basement membrane antibody; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine; D003404:Creatinine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat