Role of EDRF (nitric oxide) in diabetic renal hyperfiltration.
In order to study the role of EDRF in diabetic hyperfiltration, the concentrations of NO2-/NO3-, the stable products of nitric oxide (NO), were measured in arterial plasma, urine, and renal venous blood in streptozotocin diabetic rats and normal control rats. In additional experiments, the renal hemodynamic and blood pressure responses to graded doses of an inhibitor of NO synthesis (Nitro-L-arginine; NLA) were measured. We found that plasma and urinary levels of NO2/NO3 are significantly 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 GFR 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 significantly blunted as compared with the normal rats. Similarly, renal vascular resistance (RVR) increased less in the diabetic than in the normal rats at comparable doses of NLA. The blunted vasoconstrictor responses 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 findings suggest that NO synthesis is increased in diabetic rats manifesting hyperfiltration and are consistent with the view that excess NO synthesis contributes to renal hyperfiltration.
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Department of Medicine, Montefiore Medical Center, Bronx, New York.
Aynedjian
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D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005919:Glomerular Filtration Rate; D008297:Male; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism* / Q000502:physiology*; D009573:Nitrites / Q000378:metabolism; D019335:Nitroarginine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation
D009566:Nitrates; D009573:Nitrites; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine