Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
J Pharmacol Sci. 2013;122(2):103-8. doi: 10.1254/jphs.13045fp. Epub 2013 May 22.
Angiotensin II (Ang II) infusion into rats elevates local angiotensin II levels through an AT1 receptor-dependent pathway in the kidney. We examined whether treatment with an angiotensin-converting enzyme (ACE) inhibitor, temocapril, or an AT1-receptor blocker, olmesartan, prevented elevation of Ang II levels in the kidney of angiotensin I (Ang I)-infused rats. Rats were infused with Ang I (100 ng/min) and treated with temocapril (30 mg/kg per day, n = 10) or olmesartan (10 mg/kg per day, n = 9) for 4 weeks. Ang I infusion significantly elevated blood pressure compared with vehicle-infused rats (n = 6). Treatment with temocapril or olmesartan suppressed Ang I-induced hypertension. Temocapril suppressed both plasma and renal ACE activity. Ang I infusion increased Ang II content in the kidney. Interestingly, temocapril failed to reduce the level of Ang II in the kidney, while olmesartan markedly suppressed an increase in renal Ang II levels. These results suggest a limitation of temocapril and a benefit of olmesartan to inhibit the renal renin-angiotensin system and suggest the possible existence of an ACE inhibitor-insensitive pathway that increases Ang II levels in rat kidney.
血管紧张素 II（Ang II）输注到大鼠体内，通过肾脏中的 AT1 受体依赖性途径升高局部 Ang II 水平。我们研究了血管紧张素转换酶（ACE）抑制剂替莫普利或 AT1 受体阻滞剂奥美沙坦是否能防止血管紧张素 I（Ang I）输注大鼠肾脏中 Ang II 水平的升高。大鼠接受 Ang I（100ng/min）输注，并接受替莫普利（30mg/kg/天，n=10）或奥美沙坦（10mg/kg/天，n=9）治疗 4 周。Ang I 输注显著升高血压，与载体输注大鼠（n=6）相比。替莫普利或奥美沙坦治疗抑制 Ang I 诱导的高血压。替莫普利抑制血浆和肾脏 ACE 活性。Ang I 输注增加肾脏 Ang II 含量。有趣的是，替莫普利未能降低肾脏中 Ang II 的水平，而奥美沙坦则显著抑制肾脏 Ang II 水平的升高。这些结果表明替莫普利存在局限性，而奥美沙坦抑制肾素-血管紧张素系统具有益处，并提示大鼠肾脏中可能存在 ACE 抑制剂不敏感途径，可增加 Ang II 水平。
