Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
Biol Pharm Bull. 2009 Dec;32(12):2041-5. doi: 10.1248/bpb.32.2041.
Angiotensin II type 1 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 antihypertensive effect.
血管紧张素 II 型 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。除了降低血压的能力外，这些化合物还被报道可以保护器官，如肾脏和心脏。尽管这些保护作用的机制尚未完全阐明，但人们普遍认为其抗氧化作用可能发挥了作用。本研究旨在使用 5/6 肾切除术大鼠来描述奥美沙坦的抗氧化活性与其药理学作用（如肾保护或降压作用）之间的关系。在 5/6 肾切除术大鼠中，潜在的抗氧化能力、血液中白蛋白氧化与未氧化的比值（作为蛋白质氧化的标志物）、收缩压和舒张压、血浆肌酐浓度以及尿液中排出的蛋白质量均显著高于相应的假手术大鼠。然而，奥美沙坦在 5/6 肾切除术后 8 周内经口给药可显著抑制这些参数。奥美沙坦给药 4 周后，氧化白蛋白比值显著降低，并且在 8 周时保持较低水平。此外，奥美沙坦改善了来自大鼠血浆的分离白蛋白的自由基清除活性。有趣的是，在肾功能方面发现了氧化白蛋白比值与奥美沙坦之间存在良好的相关性，而在血压方面则没有相关性。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，而与降压作用无关。
