Role of endothelium-derived nitric oxide in the pathogenesis of the renal hemodynamic changes of experimental diabetes.
To evaluate the role of nitric oxide (NO) in diabetic hyperfiltration, renal hemodynamic changes and changes in urinary excretion of NO2/NO3 in response to the NO inhibitor nitro-L-arginine methyl ester (L-NAME) and the NO-donating agent glyceryl trinitrate (GTN) were investigated in conscious streptozocin-induced diabetic (D) and age-matched control (C) rats. In all experiments, D rats demonstrated increased glomerular filtration rate (GFR), renal plasma flow (RPF), polyuria, and an increased urinary sodium excretion when compared with C rats. An intravenous bolus of low-dose L-NAME (1 mg/kg body wt) increased modestly systolic blood pressure (sBP) in C rats but had no effect on sBP in D rats. L-NAME induced a marked decrease in GFR and RPF in D rats with no change in filtration fraction (FF). In C rats, no change in GFR was observed, and RPF decreased, resulting in a rise in FF. A supramaximal dose of L-NAME (10 mg/kg body wt) increased sBP in C and D rats to a similar degree. With high-dose L-NAME, GFR decreased in D but not in C rats. There was a greater decrease in RPF in D rats when compared with C animals. An intravenous infusion of GTN induced a modest decrease in sBP in both C and D rats (P < 0.01). There were no changes in GFR and RPF in D rats, but in the C group, GTN increased RPF (P < 0.05) with a tendency for a rise in GFR (P = 0.09). Basal urinary NO2/NO3 excretion was increased in D rats in all experiments.(ABSTRACT TRUNCATED AT 250 WORDS)
Komers
R
R
Department of Medicine, University of Melbourne, Heidelberg Repatriation Hospital, Victoria, Australia.
Allen
T J
TJ
Cooper
M E
ME
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000098:blood supply; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D005996:Nitroglycerin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects*
D009569:Nitric Oxide; D001120:Arginine; D005996:Nitroglycerin; D019331:NG-Nitroarginine Methyl Ester