Renin-angiotensin system in intestinal inflammation-Angiotensin inhibitors to treat inflammatory bowel diseases?

Basic Clin Pharmacol Toxicol. 2021 Sep;129(3):161-172. doi: 10.1111/bcpt.13624. Epub 2021 Jun 27.

Abstract

Inflammatory bowel diseases (IBDs) are chronic disorders of the gastrointestinal tract, which manifest in recurring gastrointestinal inflammation. The current treatment options of IBD are not curative and are lacking in aspects like prevention of fibrosis. New treatment options are needed to fulfil the unmet needs and provide alternatives to drugs with resistances and side effects. Drugs targeting the renin-angiotensin system (RAS), besides being antihypertensive, also possess anti-inflammatory and antifibrotic properties and could offer an inexpensive alternative to control inflammation and fibrosis in the gut. RAS inhibitors have been effective in preventing and alleviating colitis in preclinical studies, but available human data are still sparse. This review outlines the pathophysiological functions of RAS in the gut and summarizes preclinical studies utilizing pharmacological RAS inhibitors in the treatment of experimental colitis. We discuss the alterations in intestinal RAS and the available evidence of the benefits of RAS inhibitors for IBD patients. Retrospective studies comparing IBD patients using ACE inhibitors or angiotensin II receptor blockers have provided optimistic results regarding a milder disease course and fewer hospitalizations and corticosteroid use in patients using RAS inhibitors. Prospective studies are needed to evaluate the effectiveness of these promising medications in the treatment of IBD.

Keywords: ACE inhibitors; angiotensin II receptor blockers; colitis; inflammatory bowel diseases; renin-angiotensin system.

Publication types

  • Review

MeSH terms

  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Angiotensins / antagonists & inhibitors*
  • Angiotensins / pharmacology
  • Angiotensins / therapeutic use
  • Animals
  • Antihypertensive Agents / therapeutic use
  • Colitis / drug therapy
  • Drug Evaluation, Preclinical
  • Fibrosis
  • Humans
  • Hypertension / drug therapy
  • Inflammation / drug therapy*
  • Inflammatory Bowel Diseases / complications
  • Inflammatory Bowel Diseases / drug therapy*
  • Mice
  • Models, Animal
  • Renin-Angiotensin System / drug effects*
  • Retrospective Studies

Substances

  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Angiotensins
  • Antihypertensive Agents