Article Text

PDF

The renin-angiotensin system: a potential therapeutic target in ARDS?
  1. J Elder
  1. LAT Respiratory Medicine, Belfast City Hospital, Northern Ireland, UK; jenniferhelderhotmail.com

Statistics from Altmetric.com

This paper reports a critical role of the renin-angiotensin system (RAS) in the pathogenesis of acute lung injury (ALI) in the mouse. Angiotensin converting enzyme (ACE) and its counter-regulatory homologue ACE2 determine the levels of angiotensin II (ATII) within the lung. By a series of logical stepwise experiments, manipulating key components of the RAS, the authors demonstrate a pivotal role of ATII (upregulated by ACE, downregulated by ACE2) in the pathogenesis of experimentally induced ALI.

Using accepted models of ALI (acid aspiration, endotoxin, and caecal ligation and perforation induced sepsis), they examined sequentially the effects of ACE2, ACE, and ATII manipulation on the severity of the induced lung injury. ACE2 knockout mice (with upregulated ATII levels) had significantly worse ALI than wild type mice (as defined by the end points of oxygenation, compliance, vascular permeability and inflammation). Treatment with recombinant ACE2 partially protected against lung injury in both wild type and ACE2 knockout mice. Importantly, ACE2 was also downregulated in wild type mice with ALI. In contrast, ACE knockout mice (with downregulated ATII levels) were markedly protected against ALI compared with wild type mice. Finally, they showed that the deleterious effects of ATII were mediated via the ATII type 1a receptor (AT1aR) in the mouse lung. Pharmacological inhibition of AT1aR resulted in significantly improved lung function in both ACE2 knockout and wild type mice.

If these findings are confirmed in human ALI/ARDS, the RAS may offer a new therapeutic target for this devastating condition.

View Abstract

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.