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.