Role of endothelium-derived nitric oxide in the pathogenesis of the renal hemodynamic changes of experimental diabetes

Diabetes. 1994 Oct;43(10):1190-7. doi: 10.2337/diab.43.10.1190.

Abstract

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)

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Arginine / analogs & derivatives*
  • Arginine / pharmacology
  • Blood Pressure / drug effects
  • Diabetes Mellitus, Experimental / physiopathology*
  • Diabetic Nephropathies / physiopathology
  • Dose-Response Relationship, Drug
  • Glomerular Filtration Rate / drug effects*
  • Hemodynamics / drug effects
  • Kidney / blood supply
  • Male
  • NG-Nitroarginine Methyl Ester
  • Nitric Oxide / physiology*
  • Nitroglycerin / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Reference Values
  • Regional Blood Flow / drug effects
  • Renal Circulation / drug effects*

Substances

  • Nitric Oxide
  • Arginine
  • Nitroglycerin
  • NG-Nitroarginine Methyl Ester