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肾素-血管紧张素-醛固酮系统及其治疗靶点。

The renin-angiotensin-aldosterone system and its therapeutic targets.

机构信息

Cardiovascular Disease Program, Biomedicine Discovery Institute and Department of Physiology, Monash University, Melbourne, Australia.

Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands.

出版信息

Exp Eye Res. 2019 Sep;186:107680. doi: 10.1016/j.exer.2019.05.020. Epub 2019 May 23.

Abstract

The renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in the regulation of blood pressure and body fluid homeostasis and is a mainstay for the treatment of cardiovascular and renal diseases. Angiotensin II and aldosterone are the two most powerful biologically active products of the RAAS, inducing all of the classical actions of the RAAS including vasoconstriction, sodium retention, tissue remodeling and pro-inflammatory and pro-fibrotic effects. In recent years, new components of the RAAS have been discovered beyond the classical pathway that have led to the identification of depressor or so-called protective RAAS pathways and the development of novel therapies targeting this system. Moreover, dual inhibitors which block the RAAS and other systems involved in the regulation of blood pressure or targeting upstream of angiotensin II by selectively deleting liver-derived angiotensinogen, the precursor to all angiotensins, may provide superior treatment for cardiovascular and renal diseases and revolutionize RAAS-targeting therapy.

摘要

肾素-血管紧张素-醛固酮系统(RAAS)在调节血压和体液平衡方面发挥着关键作用,是治疗心血管和肾脏疾病的主要方法。血管紧张素 II 和醛固酮是 RAAS 中两种最强大的生物活性产物,可引起 RAAS 的所有经典作用,包括血管收缩、钠潴留、组织重塑以及促炎和促纤维化作用。近年来,除了经典途径之外,还发现了 RAAS 的新成分,从而确定了降压或所谓的保护性 RAAS 途径,并开发了针对该系统的新型治疗方法。此外,双重抑制剂可阻断 RAAS 以及其他参与血压调节的系统,或者通过选择性地从肝脏中去除血管紧张素原(所有血管紧张素的前体)来靶向血管紧张素 II 的上游,这可能为心血管和肾脏疾病提供更好的治疗方法,并彻底改变 RAAS 靶向治疗。

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