ROLE OF EDRF (NITRIC-OXIDE) IN DIABETIC RENAL HYPERFILTRATION

In order to study the role of EDRF in diabetic hyperfiltration, the co ncentrations of NO2-/NO3-, the stable products of nitric oxide (NO), w ere measured in arterial plasma, urine, and renal venous blood in stre ptozotocin diabetic rats and normal control rats. In additional experi ments, the renal hemodynamic and blood pressure responses to graded do ses of an inhibitor of NO synthesis (Nitro-L-arginine; NLA) were measu red. We found that plasma and urinary levels of NO2-/NO3- are signific antly higher in STZ diabetic rats (10 to 15 days) than in normal rats. Renal blood flow and GFR fell comparably in diabetic and normal rats in response to NLA infusion, although the absolute levels of RBF and G FR remained significantly higher in the diabetic rats at all doses of the inhibitor. Mean arterial blood pressure (MAP) rose in response to NLA administration, but the increase in the diabetic rats was signific antly blunted as compared with the normal rats. Similarly, renal vascu lar resistance (RVR) increased less in the diabetic than in the normal rats at comparable doses of NLA. The blunted vasoconstrictor response s to NLA were accompanied by a smaller reduction in the levels of NO2- /NO3- in the urine of the diabetic versus the normal rats. These findi ngs suggest that NO synthesis is increased in diabetic rats manifestin g hyperfiltration and are consistent with the view that excess NO synt hesis contributes to renal hyperfiltration.