The Journal of laboratory and clinical medicine
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We have investigated whether nitric oxide (NO) generation is increased in diabetes and whether specific NO synthase (NOS) isoforms are up-regulated in 4-week diabetic male Wistar rats. Glomerular filtration rate (GFR), kidney weight, and urinary nitrate (NOx) generation were measured in the following groups (n = 6): normal control animals, diabetic animals, diabetic animals given L -NIL (a selective iNOS inhibitor)(D + L -NIL), diabetic animals given L -NAME (a nonselective NOS inhibitor)(D + L -NAME), and control animals given L -NAME (C + L -NAME). Diabetes increased GFR (0.78 +/- 0.05 mL/min/100 g body wt vs 1.49 +/- 0.07 mL/min/100 g body wt, P <.01). ⋯ Inducible NOS (iNOS) and endothelial NOS (eNOS) mRNA levels measured by reverse transcription-polymerase chain reaction in diabetic rats were not changed as compared with levels in controls. Cyclic guanosine monophosphate responses to carbachol (an index of eNOS activity) in glomeruli from diabetic rats were significantly reduced as compared with those in controls, and guanylate cyclase responses to sodium nitroprusside were significantly decreased. Therefore, renal NO generation, at least via eNOS and iNOS, is not the primary cause of glomerular hyperfiltration in diabetes.