The pulmonary renin-angiotensin system.
The circulating renin-angiotensin system (RAS) has a well-described role in circulatory homeostasis. Recently, local tissue-based RAS have also been described which appear to play a key role in the injury/repair response. The expression of RAS components and the elevation of angiotensin converting enzyme in a number of interstitial lung diseases suggests the existence of a pulmonary RAS and that angiotensin II could mediate, at least in part, the response to lung injury. Activation of a local RAS within the pulmonary circulation and lung parenchyma could influence the pathogenesis of lung injury via a number of mechanisms including an increase in vascular permeability, vascular tone and fibroblast activity, and by reducing alveolar epithelial cell survival. The ability of both ACE inhibitors and angiotensin II receptor antagonists to attenuate experimental lung injury further supports a role for RAS activation and suggests these agents may be useful in the treatment of diffuse parenchymal lung disease. However, further studies are required to delineate the cell types responsible for RAS component expression in the lung and also to identify the key effector molecules of this system. The presence of common polymorphisms in RAS genes and their study in relation to specific physiological phenotypes will aid both our understanding of the role of RAS in the lung and also aid the targeting of future therapies.
Marshall
Richard P
RP
Centre for Respiratory Research, Royal Free and University College London Medical School, Rayne Institute, UK. richard.marshall@ucl.ac.uk
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000809:Angiotensins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000809:Angiotensins