Chronic inhibition of nitric oxide production aggravates diabetic nephropathy in Otsuka Long-Evans Tokushima Fatty rats.
BACKGROUND
Nitric oxide (NO) is known to play a role in diabetic nephropathy, but the molecular basis for this effect remains unclear.


METHODS
Otsuka Long-Evans Tokushima Fatty spontaneous diabetic rat models were used along with Long-Evans Tokushima Otuska rat models as age-matched controls. Either L-arginine (a NO precursor) or L-NAME (a nitric oxide synthase inhibitor) was administered from the age of 22 weeks. Clinical parameters and serum and urinary NO2+NO3 levels were measured, in addition to renal histological findings and ED-1-positive cell counts in glomeruli.


RESULTS
There were no significant differences in creatinine clearance between any of the groups at any point. The levels of urinary NO2+NO3 in the diabetic group were significantly lower than those in the control groups after 40 weeks; that in the L-NAME diabetic group was significantly lower than in the other diabetic groups at 52 weeks. Compared with the other diabetic groups, the L-NAME diabetic group had significantly higher urinary protein excretion levels, histological scores, and numbers of ED-1-positive cells in glomeruli. Diabetic rats administered L-arginine excreted more urinary protein than the diabetic controls.


CONCLUSIONS
Diabetic nephropathy was exacerbated drastically by a nitric oxide synthase inhibitor and mildly by a NO precursor. These data suggested that NO may modify type 2 diabetic nephropathy in Otuska Long-Evans Tokushima Fatty rats through factors other than hemodynamics.
Kamijo
Hiroshi
H
Second Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
Higuchi
Makoto
M
Hora
Kazuhiko
K
D000818:Animals; D001120:Arginine; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism* / Q000652:urine; D003928:Diabetic Nephropathies / Q000097:blood / Q000378:metabolism* / Q000652:urine; D004791:Enzyme Inhibitors; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester; D009566:Nitrates / Q000097:blood / Q000652:urine; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009573:Nitrites / Q000097:blood / Q000652:urine; D011507:Proteinuria / Q000097:blood / Q000378:metabolism* / Q000652:urine; D051381:Rats; D020334:Rats, Inbred OLETF; D013997:Time Factors
D004791:Enzyme Inhibitors; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester