Evaluation for Antioxidant and Renoprotective Activity of Olmesartan Using Nephrectomy Rats

Angiotensin II type I receptor blockers, which inhibit the rennin-angiotensin system, are used in the treatment of hypertension. In addition to their ability to lower blood pressure, these compounds have also been reported to protect organs, such as kidney and heart. Although the mechanisms of these protective effects are not fully understood, it is generally thought that their antioxidant effects likely play a role. The aim of the present study was to characterize the relationship between the antioxidant activity of olmesartan and its pharmacological actions such as renoprotective or blood pressure lowering effects, using 5/6 nephrectomy rats. In 5/6 nephrectomy rats, the potential antioxidant power, the ratio of oxidized to unoxidized albumin, as a marker of protein oxidation in blood, both systolic and diastolic blood pressure, plasma creatinine concentration, and amounts of protein excreted into the urine were significantly higher than the corresponding values for sham operated rats. However, olmesartan significantly suppressed these parameters within 8 weeks after oral administration in 5/6 nephrectomy rats. The oxidized albumin ratio was significantly decreased 4 weeks after the administration of olmesartan and these lower levels were maintained at 8 weeks. Furthermore, olmesartan improved radical scavenging activity of isolated albumin from rat plasma. Interestingly, a good correlation was found between the oxidized albumin ratios and renal function, whereas no correlation was found in the case of blood pressure. Based on those findings, we conclude that the antioxidant properties of olmesartan may be related to its renoprotective action rather than an anti hypertensive effect.

血管紧张素II 1型受体阻滞剂可抑制肾素 - 血管紧张素系统，用于治疗高血压。除了具有降低血压的能力外，据报道这些化合物还可保护器官，如肾脏和心脏。尽管这些保护作用的机制尚未完全清楚，但一般认为它们的抗氧化作用可能起到了一定作用。本研究旨在利用5/6肾切除大鼠来描述奥美沙坦的抗氧化活性与其药理作用（如肾保护作用或降低血压作用）之间的关系。在5/6肾切除大鼠中，潜在抗氧化能力、作为血液中蛋白质氧化标志物的氧化型与未氧化型白蛋白的比值、收缩压和舒张压、血浆肌酐浓度以及尿蛋白排泄量均显著高于假手术大鼠的相应值。然而，奥美沙坦在5/6肾切除大鼠口服给药8周内显著抑制了这些参数。奥美沙坦给药4周后氧化型白蛋白比值显著降低，且这种较低水平在8周时仍得以维持。此外，奥美沙坦提高了从大鼠血浆中分离出的白蛋白的自由基清除活性。有趣的是，发现氧化型白蛋白比值与肾功能之间存在良好的相关性，而与血压之间未发现相关性。基于这些发现，我们得出结论：奥美沙坦的抗氧化特性可能与其肾保护作用有关，而非与降压作用有关。