Therapeutic potential of targeting the renin angiotensin system in portal hypertension

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.