Nussberger Jürg, Koike Hiroyuki
Division of Hypertension and Vascular Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Clin Ther. 2004;26 Suppl A:A12-20. doi: 10.1016/s0149-2918(04)90141-5.
The orally active, nonpeptide antagonists of the angiotensin II subtype 1 (AT1) receptor represent a recent class of antihypertensive drugs that selectively block the renin-angiotensin system. Olmesartan medoxomil is the newest member of this class.
This article reviews the renin-angiotensin system and how this system can be pharmacologically inhibited by the selective antagonists of the AT1 receptor, with a main focus on the AT1 receptor antagonist olmesartan.
Key studies were selected from previous work to illustrate the antihypertensive, cardioprotective, and renoprotective effects of olmesartan, and to compare class effects of AT1 receptor antagonists and angiotensin-converting enzyme (ACE) inhibitors.
Olmesartan, the active metabolite of olmesartan medoxomil, is a highly potent antagonist of the AT1 receptor. It inhibits the contractile responses to angiotensin II in guinea pig aorta, inhibits the pressor responses to angiotensin II in rats and dogs, and exhibits dose-dependent antihypertensive effects in spontaneously hypertensive rats. In addition to its antihypertensive effects, olmesartan medoxomil provides protection against cardiac and renal damage in animal models. AT1 receptor antagonists are more specific inhibitors of the renin-angiotensin system compared with ACE inhibitors. They are well tolerated and have an excellent safety profile. Unlike angiotensin-converting enzyme inhibitors, AT1 receptor antagonists lack the nonangiotensin-related side effects such as cough and angioedema.
AT1 receptor antagonists such as olmesartan represent a valid therapeutic option for the treatment of hypertension and other cardiovascular and renal diseases.
血管紧张素II 1型（AT1）受体的口服活性非肽拮抗剂是一类新型的抗高血压药物，可选择性阻断肾素-血管紧张素系统。奥美沙坦酯是该类药物的最新成员。
本文综述肾素-血管紧张素系统以及该系统如何被AT1受体选择性拮抗剂进行药理学抑制，主要聚焦于AT1受体拮抗剂奥美沙坦。
从以往的研究中选取关键研究，以阐明奥美沙坦的抗高血压、心脏保护和肾脏保护作用，并比较AT1受体拮抗剂与血管紧张素转换酶（ACE）抑制剂的类效应。
奥美沙坦酯的活性代谢产物奥美沙坦是一种高效的AT1受体拮抗剂。它可抑制豚鼠主动脉对血管紧张素II的收缩反应，抑制大鼠和犬对血管紧张素II的升压反应，并在自发性高血压大鼠中呈现剂量依赖性的降压作用。除降压作用外，奥美沙坦酯在动物模型中还可预防心脏和肾脏损伤。与ACE抑制剂相比，AT1受体拮抗剂是肾素-血管紧张素系统更具特异性的抑制剂。它们耐受性良好，安全性极佳。与血管紧张素转换酶抑制剂不同，AT1受体拮抗剂没有咳嗽和血管性水肿等非血管紧张素相关的副作用。
奥美沙坦等AT1受体拮抗剂是治疗高血压及其他心血管和肾脏疾病的有效治疗选择。
