Early effects of diabetes on inducible nitric oxide synthase in the kidney.
NO may be responsible for the glomerular hyperfiltration observed in diabetic kidney by inducing vasodilation of the afferent arteriole. The aim of this study was to evaluate which isoform of nitric oxide synthase (NOS) is responsible for increased renal production of NO in diabetic kidney. Thirty male WKY rats were divided into 6 groups. Five rats were sacrificed immediately, five after 20 days. In the other rats, diabetes was induced by streptozotocin. The four diabetic groups were sacrificed respectively after 5, 10, 15 and 20 days. Urine excretion of NO metabolites was assayed; immunochemistry showed the presence of inducible (iNOS) and endothelial constitutive (ecNOS) synthases in the kidney. Urinary excretion of NO metabolites increased significantly in diabetic rats five days after the induction of diabetes and at the end of the study whereas it was unchanged in the control group. Renal ecNOS remained unchanged throughout the study in all rats whereas iNOS increased significantly in diabetic rats from the fifth day until the end of the study. The results demonstrate that iNOS is activated in the kidney of rats, soon after the induction of diabetes, thus suggesting its involvement in the increased production of NO observed immediately after the onset of diabetes.
Department of Clinical Medicine and Neurology, Cattinara Hospital, University of Trieste, Italy.
A
A
Cosenzi
E
E
Bernobich
M
M
Bonavita
R
R
Trevisan
G
G
Bellini
L
L
Campanacci
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology* / Q000652:urine; D007150:Immunohistochemistry; D007668:Kidney / Q000201:enzymology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism* / Q000652:urine; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D051381:Rats; D011921:Rats, Inbred WKY; D012016:Reference Values
D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat