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

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 NO X production to a rate 3 times that observed during incubation with normal glucose ( P P P 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.