High glucose augments arginase activity and nitric oxide production in the renal cortex

Naohito Ishii, Hideki Ikenaga, Pamela K. Carmines, Yoshikazu Aoki, Zensuke Ogawa, Takao Saruta, Tetsuya Suga

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Abstract

To clarify the interaction between arginase and nitric oxide (NO) production in the kidney with normal and high glucose levels, renal cortical slices from male Sprague-Dawley rats were incubated in Hank's solution containing various concentrations of L-norvaline (Nval; an arginase inhibitor), 500 U/mL superoxide dismutase, and either 5 mmol/L (normal) or 20 mmol/L (high) glucose (n = 5 per group). Incubation with Nval increased renal cortical NO X (nitrite + nitrate) production dose-dependently, indicating competition between arginase and NO synthase (NOS) for the substrate (L-arginine). In the basal condition without Nval, high glucose also increased NOX production to a rate 3 times that observed during incubation with normal glucose (P < .01). This effect of high glucose was not altered by Nval. Rather, the effects of high glucose and Nval were additive, indicating that the activity of NOS per se is enhanced by high glucose. Direct assay of arginase and NOS activities confirmed stimulation of both enzymes under the high glucose condition (P < .05, P < .01, v normal glucose, respectively). However, high glucose did not change the amount of L-arginine present in renal cortical slices. These data reveal that arginase competes with NOS for L-arginine in the renal cortex, and that high glucose increases the activity of both enzymes without affecting the amount of substrate. These results suggest that increased NOS activity, rather than altered substrate availability, may be the principal factor underlying increased NO synthesis in diabetic kidneys.

Original languageEnglish (US)
Pages (from-to)868-874
Number of pages7
JournalMetabolism: Clinical and Experimental
Volume53
Issue number7
DOIs
StatePublished - Jul 1 2004

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Arginase
Nitric Oxide
Kidney
Glucose
Nitric Oxide Synthase
Arginine
Enzymes
Nitrites
Nitrates
Superoxide Dismutase
Sprague Dawley Rats

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

High glucose augments arginase activity and nitric oxide production in the renal cortex. / Ishii, Naohito; Ikenaga, Hideki; Carmines, Pamela K.; Aoki, Yoshikazu; Ogawa, Zensuke; Saruta, Takao; Suga, Tetsuya.

In: Metabolism: Clinical and Experimental, Vol. 53, No. 7, 01.07.2004, p. 868-874.

Research output: Contribution to journalArticle

Ishii, Naohito ; Ikenaga, Hideki ; Carmines, Pamela K. ; Aoki, Yoshikazu ; Ogawa, Zensuke ; Saruta, Takao ; Suga, Tetsuya. / High glucose augments arginase activity and nitric oxide production in the renal cortex. In: Metabolism: Clinical and Experimental. 2004 ; Vol. 53, No. 7. pp. 868-874.
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