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

• Published in: Metabolism, clinical and experimental Vol. 53; no. 7; pp. 868 - 874
• Main Authors: Ishii, Naohito, Ikenaga, Hideki, Carmines, Pamela K, Aoki, Yoshikazu, Ogawa, Zensuke, Saruta, Takao, Suga, Tetsuya
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.07.2004; Elsevier
• Subjects: Animals; Arginase - antagonists & inhibitors; Arginase - metabolism; Arginine - metabolism; Biological and medical sciences; Carbohydrates; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; Glucose - pharmacology; In Vitro Techniques; Kidney Cortex - drug effects; Kidney Cortex - metabolism; Male; Metabolisms and neurohumoral controls; Nitric Oxide - biosynthesis; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase Type III; Protein Biosynthesis; Rats; Rats, Sprague-Dawley; Valine - analogs & derivatives; Valine - pharmacology; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Enzyme; Nitric oxide; Production; Hydrolases; Activity; Arginase; Glucose; Kidney
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/j.metabol.2004.02.011

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 NO X 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.