Pathways of hepatic and renal damage through non‐classical activation of the renin‐angiotensin system in chronic liver disease

摘要: In liver cirrhosis, renin-angiotensin system (RAS) activation sustains renal sodium retention and hepatic fibrogenesis. New information has recently enlivened the traditional concept of RAS. For instance, renin prorenin bind their ubiquitous receptors, resulting in local production angiotensin (Ang) II; increased serum calcium calcimimetic agents, through stimulation extracellular calcium-sensing receptors (CaSR), blunt lead to natriuretic effects human experimental cirrhosis. Alongside systemic production, there is Ang II tissue within various organs RAS enzymes different from angiotensin-converting enzyme (ACE), that chymase, plasminogen activator several cathepsins. inhibition chymase leads antifibrotic effects, without changes haemodynamics. kidney, coordinates proximal distal tubular reabsorption. However, renalase, whose plasma levels are severely altered degrades tubule catecholamines, antagonizing Angiotensinogen-derived vasodilating peptides (Ang1-9, Ang1-7, Ang3-8) have been described. Receptor agonists or antagonists available affect portal hypertension ACE2-dependent generation Ang1-7 may inhibit fibrosis. clearance by means neprilysin blockade hypotensive effects. Ang1-12, does not regulate, converted via chymase. Finally, behaves as either an antinatriuretic a agent, based on content AT1 R AT2 ratio being prone pharmacological modulation.