Objectives:Experiments evaluated the hypothesis that angiotensin-converting enzyme (ACE) inhibition suppresses hyperglycemia-induced nitrotyrosine (NT) production in the renal cortex.Design and methods:
Rats were untreated (UNTR, n = 6) or received the ACE inhibitor enalapril (20 mg/kg/day; ENAL, n = 6) for 2 weeks. Renal cortical slices were incubated for 90 min in media containing 5 (normal) or 20 mmol/L (high) glucose. Superoxide anion (O2·−) and nitrate + nitrite (NOX) levels were measured in the media. Superoxide dismutase (SOD) activity and NT content were measured in the tissue homogenate.
Results:
In the UNTR group, high glucose increased O2·− and NOX production by the renal cortex (P < 0.05 vs. normal glucose). Likewise, NT content and SOD activity of the renal cortex augmented (P < 0.05 vs. normal glucose). In the ENAL group, O2·− production and NT content were glucose-insensitive, but high glucose exerted an exaggerated impact on NOX production and SOD activity (P < 0.01 vs. UNTR in high glucose).
Conclusion:
Accelerated NT content in the renal cortex during high-glucose conditions was prevented by ACE inhibitor treatment. It was suggested that, apart from its anti-hypertensive effect, the mechanism of suppressed NT degradation in the renal cortex by the ACE inhibitor enhances both O2·− degradation per se and antioxidative effects including SOD activation.
