Renal neuronal nitric oxide synthase protein expression as a marker of renal injury.
BACKGROUND
Animal studies suggest that nitric oxide deficiency occurs in the remnant after 5/6 removal of renal mass. The present studies investigated the time course in relation to progression of renal disease, as well as the impact on individual renal nitric oxide synthase (NOS) isoforms.


METHODS
Rats were studied from 2 to 11 weeks after 5/6 ablation/infarction (A/I) of renal mass, with acceleration of progression by high protein and salt intake, in some groups. Measurements were made before sacrifice of 24-hour protein and creatinine excretion, blood was taken for creatinine and blood urea nitrogen (BUN) determination and the kidneys were investigated histologically for structural damage, abundance of endothelial NOS (eNOS) and neuronal NOS (nNOS), and in some groups for in vitro NOS activity.


RESULTS
A time-dependent fall in glomerular filtration rate (GFR) and rise in proteinuria and glomerular sclerosis developed after 5/6 A/I. The nNOS abundance in cortex and medulla was decreased relative to shams, in all but the mildest injury and there was a strong, steep correlation between level of glomerular sclerosis and the degree of reduction in renal nNOS. Where measured, cortical NOS activity correlated with the nNOS abundance. In contrast, the eNOS abundance was either increased or unchanged in rats post A/I.


CONCLUSIONS
Renal nNOS abundance was reduced in the 5/6 A/I model of renal disease when plasma creatinine> approximately 1 mg/dL and when> approximately 20% of remaining glomeruli were sclerosed.
Szabo
Attila J
AJ
Department of Physiology, West Virginia University, Morgantown, West Virginia 26506, USA.
Wagner
Laszlo
L
Erdely
Aaron
A
Lau
Kim
K
Baylis
Chris
C
D000818:Animals; D015415:Biomarkers; D003404:Creatinine / Q000378:metabolism; D007668:Kidney / Q000201:enzymology*; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D011507:Proteinuria / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D014511:Uremia / Q000378:metabolism*
D015415:Biomarkers; D003404:Creatinine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; C496322:Nos1 protein, rat; C496316:Nos3 protein, rat