Therapeutic effects of angiotensin (AT1) receptor antagonists: Potential contribution of mechanisms other than AT1 receptor blockade

被引：18

作者：

Schmidt B. ^{[1
]}

Drexler H. ^{[2
]}

Schieffer B. ^{[2
,3
]}

机构：

[1] Institute for Organic Chemistry, Technische Universitat Darmstadt, Darmstadt

[2] Department of Cardiology/Angiology, Medizinische Hochschule, Hannover

[3] Hannover 30625

来源：

American Journal of Cardiovascular Drugs | 2004年 / 4卷 / 6期

关键词：

Growth Hormone; High Performance Liquid Chromatography; Losartan; Valsartan; Irbesartan;

D O I：

10.2165/00129784-200404060-00004

中图分类号：

学科分类号：

摘要：

Blockade of the renin-angiotensin system improves morbidity and mortality of patients with cardiovascular diseases, e.g. arterial hypertension, renal failure, following myocardial infarction and in congestive heart failure. The angiotensin II type 1 (AT1) receptor antagonists (angiotensin receptor blockers; ARBs), i.e. losartan, eprosartan, irbesartan and valsartan were developed by computer-based molecule design. Early observations already indicate that the ARBs elicit pleiotropic effects developing anti-aggregatory, anti-inflammatory and anti-mitogenic effects independent from their actions at the AT1 receptor. Losartan metabolism indicates a number of known active intermediates and pointed to further interactions of these derivatives with other receptors and cellular signaling systems. Here we discuss a compilation of detailed pharmacokinetic and pharmacodynamic data of active metabolites of ARBs indicating their mode of action and suggest novel therapeutic implications. The clinical observations that ARBs elicit potencies in patients with cardiovascular diseases via the regulation of inflammatory, growth and homeostatic factors lead us to focus on specific, reactive metabolites, which hold potential for future indications and possible drug interactions in cardiovascular diseases. © 2004 Adis Data Information BV. All rights reserved.

引用

页码：361 / 368

页数：7

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