Impact of angiotensin-converting enzyme inhibition on renal cortical nitrotyrosine content during increased extracellular glucose concentration

Abstract

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 (O 2 ·−) and nitrate + nitrite (NO X ) 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 O 2 ·− and NO X 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, O 2 ·− production and NT content were glucose-insensitive, but high glucose exerted an exaggerated impact on NO X 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 O 2 ·− degradation per se and antioxidative effects including SOD activation.