Liver disease and the renin–angiotensin system: Recent discoveries and clinical implications
- 18 August 2008
- journal article
- review article
- Published by Wiley in Journal of Gastroenterology and Hepatology
- Vol. 23 (9), 1327-1338
- https://doi.org/10.1111/j.1440-1746.2008.05461.x
Abstract
The renin–angiotensin system (RAS) is a key regulator of vascular resistance, sodium and water homeostasis and the response to tissue injury. Historically, angiotensin II (Ang II) was thought to be the primary effector peptide of this system. Ang II is produced predominantly by the effect of angiotensin converting enzyme (ACE) on angiotensin I (Ang I). Ang II acts mainly through the angiotensin II type‐1 receptor (AT1) and, together with ACE, these components represent the ‘classical’ axis of the RAS. Drug therapies targeting the RAS by inhibiting Ang II formation (ACE inhibitors) or binding to its receptor (angiotensin receptor blockers) are now in widespread clinical use and have been shown to reduce tissue injury and fibrosis in cardiac and renal disease independently of their effects on blood pressure. In 2000, two groups using different methodologies identified a homolog of ACE, called ACE2, which cleaves Ang II to form the biologically active heptapeptide, Ang‐(1–7). Conceptually, ACE2, Ang‐(1–7), and its putative receptor, the mas receptor represent an ‘alternative’ axis of the RAS capable of opposing the often deleterious actions of Ang II. Interestingly, ACE inhibitors and angiotensin receptor blockers increase Ang‐(1–7) production and it has been proposed that some of the beneficial effects of these drugs are mediated through upregulation of Ang‐(1–7) rather than inhibition of Ang II production or receptor binding. The present review focuses on the novel components and pathways of the RAS with particular reference to their potential contribution towards the pathophysiology of liver disease.Keywords
This publication has 118 references indexed in Scilit:
- Upregulation of hepatic angiotensin-converting enzyme 2 (ACE2) and angiotensin-(1–7) levels in experimental biliary fibrosisJournal of Hepatology, 2007
- AT1 receptor antagonist Candesartan in selected cirrhotic patients: Effect on portal pressure and liver fibrosis markersJournal of Hepatology, 2007
- Circulating Activities of Angiotensin-Converting Enzyme, Its Homolog, Angiotensin-Converting Enzyme 2, and Neprilysin in a Family StudyHypertension, 2006
- Anti-fibrogenic function of angiotensin II type 2 receptor in CCl4-induced liver fibrosisBiochemical and Biophysical Research Communications, 2006
- Combined effect of an ACE inhibitor, perindopril, and interferon on liver fibrosis markers in patients with chronic hepatitis CThe Esophagus, 2005
- Anti-fibrogenic effects of captopril and candesartan cilexetil on the hepatic fibrosis development in rat: The effect of AT1-R blocker on the hepatic fibrosisExperimental and Toxicologic Pathology, 2003
- Captopril reduces portal pressure effectively in portal hypertensive patients with low portal venous velocityThe Esophagus, 2003
- Angiotensin IV in the central nervous systemCell and tissue research, 2003
- Angiotensin-(1-7) Inhibits Vascular Smooth Muscle Cell GrowthHypertension, 1996
- Diagnostic Significance of Serum Angiotensin-Converting Enzyme Activity in Biochemical Tests with Special Reference to Chronic Liver Diseases.Japanese Journal of Medicine, 1991