Ishii Naohito, Ikenaga Hideki, Carmines Pamela K, Takada Nobukazu, Okazaki Toshio, Nagai Tatsuo, Maeda Tadakazu, Aoki Yoshikazu, Saruta Takao, Katagiri Masato
Department of Clinical Physiology, Kitasato University School of Allied Health Sciences, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan.
Clin Biochem. 2006 Jun;39(6):633-9. doi: 10.1016/j.clinbiochem.2006.02.005. Epub 2006 Apr 21.
Experiments evaluated the hypothesis that angiotensin-converting enzyme (ACE) inhibition suppresses hyperglycemia-induced nitrotyrosine (NT) production in the renal cortex.
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 (NO(X)) levels were measured in the media. Superoxide dismutase (SOD) activity and NT content were measured in the tissue homogenate.
In the UNTR group, high glucose increased O2*- 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, O2*- 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).
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.
实验评估了血管紧张素转换酶（ACE）抑制可抑制高血糖诱导的肾皮质硝基酪氨酸（NT）生成这一假说。
大鼠未接受治疗（未治疗组，n = 6）或接受ACE抑制剂依那普利（20 mg/kg/天；依那普利组，n = 6）治疗2周。肾皮质切片在含有5（正常）或20 mmol/L（高）葡萄糖的培养基中孵育90分钟。测量培养基中的超氧阴离子（O2*-）和硝酸盐+亚硝酸盐（NO(X)）水平。测量组织匀浆中的超氧化物歧化酶（SOD）活性和NT含量。
在未治疗组中，高糖增加了肾皮质的O2*-和NO(X)生成（与正常葡萄糖相比，P < 0.05）。同样，肾皮质的NT含量和SOD活性增加（与正常葡萄糖相比，P < 0.05）。在依那普利组中，O2*-生成和NT含量对葡萄糖不敏感，但高糖对NO(X)生成和SOD活性有更大影响（与高糖条件下的未治疗组相比，P < 0.01）。
ACE抑制剂治疗可防止高糖条件下肾皮质中NT含量的加速增加。提示ACE抑制剂除具有抗高血压作用外，其抑制肾皮质中NT降解的机制可增强O2*-本身的降解以及包括SOD激活在内的抗氧化作用。
