Review article: the pathophysiological roles of the renin-angiotensin system in the gastrointestinal tract

Abstract

Background: The renin-angiotensin system (RAS) is a homeostatic pathway widely known to regulate cardiovascular and renal physiology; however, little is known about its influence in gastrointestinal tissues.

Aim: To elicit the anatomical distribution and physiological significance of the components of the RAS in the gastrointestinal tract.

Methods: An extensive online literature review including Pubmed and Medline.

Results: There is evidence for RAS involvement in gastrointestinal physiology and pathophysiology, with all the components required for autonomous regulation identified throughout the gastrointestinal tract. The RAS is implicated in the regulation of glucose, amino acid, fluid and electrolyte absorption and secretion, motility, inflammation, blood flow and possibly malignant disease within the gastrointestinal tract. Animal studies investigating the effects of RAS blockade in a range of conditions including inflammatory bowel disease, functional gut disorders, gastrointestinal malignancy and even intestinal ischaemia have been encouraging to date. Given the ready availability of drugs that modify the RAS and their excellent safety profile, an opportunity exists for investigation of their possible therapeutic role in a variety of human gastrointestinal diseases.

Conclusions: The gastrointestinal renin-angiotensin system appears to be intricately involved in a number of physiological processes, and provides a possible target for novel investigative and therapeutic approaches.

Figure 1

The contemporary renin‐angiotensin system (RAS). ACE, angiotensin converting enzyme; NEP, neutral endopeptidase; Am, aminopeptidase; AT1R, angiotensin type 1 receptor; AT2R, angiotensin type 2 receptor; AT4R, angiotensin type 4 receptor; PRR, (pro)renin receptor.

Figure 2

Distribution of components of the RAS in the gastrointestinal tract. Diagrammatic representation of RAS components in (a) small intestine, (b) colon, (c) stomach and (d) oesophagus.