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

Radko Komers, Terri J. Allen, Mark E. Cooper

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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. A decrease in urinary NO2/NO3 levels was observed after low-dose L-NAME in D rats, with a similar trend after high-dose L-NAME. No such changes were observed in C rats. GTN infusion had no effect on urinary NO2/NO3 excretion in D rats but increased urinary NO2/NO3 levels in C rats to levels that were not statistically different from those in D rats. These studies suggest that increased renal production and/or sensitivity to endothelium-derived relaxing factor/NO may play a role in the genesis of diabetic hyperfiltration.

Original languageEnglish (US)
Pages (from-to)1190-1197
Number of pages8
JournalDiabetes
Volume43
Issue number10
StatePublished - 1994
Externally publishedYes

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Nitric Oxide
Hemodynamics
Kidney
Renal Plasma Flow
NG-Nitroarginine Methyl Ester
Glomerular Filtration Rate
Blood Pressure
Nitroglycerin
Endothelium-Dependent Relaxing Factors
Polyuria
Streptozocin
Intravenous Infusions
Sodium

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

Cite this

Role of endothelium-derived nitric oxide in the pathogenesis of the renal hemodynamic changes of experimental diabetes. / Komers, Radko; Allen, Terri J.; Cooper, Mark E.

In: Diabetes, Vol. 43, No. 10, 1994, p. 1190-1197.

Research output: Contribution to journalArticle

Komers, Radko ; Allen, Terri J. ; Cooper, Mark E. / Role of endothelium-derived nitric oxide in the pathogenesis of the renal hemodynamic changes of experimental diabetes. In: Diabetes. 1994 ; Vol. 43, No. 10. pp. 1190-1197.
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