Carson P, Giles T, Higginbotham M, Hollenberg N, Kannel W, Siragy H M
Department of Cardiology, Veterans Affairs Medical Center, Washington, DC, USA.
Clin Cardiol. 2001 Mar;24(3):183-90. doi: 10.1002/clc.4960240303.
Hypertension is a major problem throughout the developed world. Although current antihypertensive treatment regimens reduce morbidity and mortality, patients are often noncompliant, and medications may not completely normalize blood pressure. As a result, current therapy frequently does not prevent or reverse the cardiovascular remodeling that often occurs when blood pressure is chronically elevated. Blockade of the renin-angiotensin system (RAS) is effective in controlling hypertension and treating congestive heart failure. Both angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) inhibit the activity of the RAS, but these two classes of antihypertensive medications have different mechanisms of action and different pharmacologic profiles. Angiotensin-converting enzyme inhibitors block a single pathway in the production of angiotensin II (Ang II). In addition, angiotensin I is not the only substrate for ACE. The ACE inhibitors also block the degradation of bradykinin that may have potential benefits in cardiovascular disease. Bradykinin is, however, the presumed cause of cough associated with ACE inhibitor therapy. Data from clinical trials on ACE inhibitors serve to support the involvement of the RAS in the development of cardiovascular disease. Angiotensin receptor blockers act distally in the RAS to block the Ang II type 1 (AT1) receptor selectively. Thus, ARBs are more specific agents and avoid many side effects. Experimental and clinical trials have documented the efficacy of ARBs in preserving target-organ function and reversing cardiovascular remodeling. In some instances, maximal benefit may be obtained with Ang II blockade using both ARBs and ACE inhibitors. This review describes clinical trials that document the efficacy of ARBs in protecting the myocardium, blood vessels, and renal vasculature.
高血压是整个发达国家面临的一个主要问题。尽管目前的抗高血压治疗方案可降低发病率和死亡率,但患者常常不依从治疗,而且药物可能无法使血压完全恢复正常。因此,当前的治疗常常无法预防或逆转血压长期升高时经常发生的心血管重塑。肾素 - 血管紧张素系统(RAS)的阻断在控制高血压和治疗充血性心力衰竭方面是有效的。血管紧张素转换酶(ACE)抑制剂和血管紧张素受体阻滞剂(ARB)都能抑制RAS的活性,但这两类抗高血压药物具有不同的作用机制和不同的药理学特性。血管紧张素转换酶抑制剂阻断血管紧张素II(Ang II)产生过程中的单一途径。此外,血管紧张素I并非ACE的唯一底物。ACE抑制剂还阻断缓激肽的降解,这可能对心血管疾病具有潜在益处。然而,缓激肽被认为是与ACE抑制剂治疗相关咳嗽的原因。关于ACE抑制剂的临床试验数据支持RAS参与心血管疾病的发生发展。血管紧张素受体阻滞剂在RAS的下游起作用,选择性地阻断1型血管紧张素II(AT1)受体。因此,ARB是更具特异性的药物,可避免许多副作用。实验和临床试验已证明ARB在保护靶器官功能和逆转心血管重塑方面的疗效。在某些情况下,联合使用ARB和ACE抑制剂进行Ang II阻断可能会获得最大益处。这篇综述描述了证明ARB在保护心肌、血管和肾血管系统方面疗效的临床试验。