TY - JOUR T1 - Angiotensin converting enzyme inhibitors and angiotensin II antagonists as therapy in chronic liver disease JF - Gut JO - Gut SP - 303 LP - 308 DO - 10.1136/gut.49.2.303 VL - 49 IS - 2 AU - J VLACHOGIANNAKOS AU - A K W TANG AU - D PATCH AU - A K BURROUGHS Y1 - 2001/08/01 UR - http://gut.bmj.com/content/49/2/303.abstract N2 - Portal hypertension is the major complication of chronic liver disease and is associated with reduced survival.1Pharmacological treatment is based on the premise that a sustained reduction in portal pressure will reduce the consequences of portal hypertension—that is, variceal bleeding, hepatic encephalopathy, and development of ascites.2 Non-selective β-blockers have proved effective in reducing portal pressure by lowering splanchnic blood inflow3 and are used in primary and secondary prevention of variceal bleeding.4 ,5 However, the mean decrease in portal pressure in response to propranolol is only approximately 15%6 and one third of cirrhotic patients do not respond despite adequate blockade.7 During the last decade, increased knowledge of the pathophysiology of portal hypertension has resulted in the use of new pharmacological targets; most importantly for the reduction of intrahepatic resistance, which is now recognised to be due in part to activated stellate cell contraction (myofibroblasts). These represent mesenchymal cells that reside in the perisinusoidal space of Disse and resemble tissue pericytes, a cell type with smooth muscle features that is thought to regulate blood flow via pericapillary constriction.8During liver injury they undergo “activation”, characterised by production of increased amounts of extracellular matrix and are responsible for fibrosis.9 Moreover, experimental data provide strong evidence that activated stellate cells are contractile and may regulate sinusoidal blood flow, especially in the injured liver.10 The renin-angiotensin-aldosterone system (RAAS) is usually activated in patients with liver cirrhosis and this represents a homeostatic response to counterbalance the vasodilatation, arterial hypotension, and renal hypoperfusion observed in portal hypertension.11Plasma renin activity (PRA) is elevated in cirrhotics and is correlated with the hepatic venous pressure gradient (HVPG).12Angiotensin II (ANG-II) is considered a potential mediator of intrahepatic portal hypertension because its plasma levels are elevated in cirrhosis, … ER -