Review
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World J Gastrointest Pathophysiol. Feb 15, 2013; 4(1): 1-11
Published online Feb 15, 2013. doi: 10.4291/wjgp.v4.i1.1
Therapeutic potential of targeting the renin angiotensin system in portal hypertension
Chandana B Herath, Josephine A Grace, Peter W Angus
Chandana B Herath, Josephine A Grace, Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria 3084, Australia
Josephine A Grace, Peter W Angus, Department of Gastroenterology, Austin Health, Heidelberg, Victoria 3084, Australia
Author contributions: Herath CB wrote and reviewed the manuscript; Grace JA contributed to the work and reviewed the manuscript; Angus PW reviewed and assisted with editing the manuscript.
Supported by Grant from the National Health and Medical Research Council of Australia
Correspondence to: Chandana B Herath, PhD, Department of Medicine, University of Melbourne, Austin Health, 145 Studley Road, Heidelberg, Victoria 3084, Australia. cherath@unimelb.edu.au
Telephone: +61-3-94962549 Fax: +61-3-94575485
Received: September 24, 2012
Revised: November 15, 2012
Accepted: January 5, 2013
Published online: February 15, 2013
Processing time: 191 Days and 3 Hours
Abstract

Portal hypertension is responsible for the bulk of the morbidity and mortality in patients with cirrhosis. Drug therapy to reduce portal pressure involves targeting two vascular beds. The first approach is to reduce intra hepatic vascular tone induced by the activity of powerful vasocontrictors such as angiotensin II, endothelin-1 and the sympathetic system and mediated via contraction of perisinusoidal myofibroblasts and pervascular smooth muscle cells. The second approach is to reduce mesenteric and portal blood flow. Non-selective β-blockers are widely used and have been shown to prolong patient survival and reduce oesophageal variceal bleeding in advanced cirrhosis. However many patients are unable to tolerate these drugs and they are ineffective in a significant proportion of patients. Unfortunately there are no other drug therapies that have proven efficacy in the treatment of portal hypertension and prevention of variceal bleeding. This review briefly outlines current therapeutic approaches to the management of portal hypertension, and the evidence supporting the role of the renin angiotensin system (RAS) and the use of RAS blockers in this condition. It will also outline recent advances in RAS research that could lead to the development of new treatments focusing in particular on the recently discovered “alternate axis” of the RAS.

Keywords: Angiotensin-(1-7); Portal hypertension; Intrahepatic resistance; Mesenteric vasodilatation; Variceal bleeding; Non-selective β-blockers; Renin angiotensin system; Mas receptor; Angiotensin receptor; Cirrhosis