Cited by 61Renin-Angiotensin System StudiesLiver Disease and TransplantationLiver physiology and pathology

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

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Sansoè, Giovanni, Aragno, Manuela, Wong, Florence·2020·Liver International

Abstract

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 and prorenin bind their ubiquitous receptors, resulting in the local production of angiotensin (Ang) II; increased serum calcium and calcimimetic agents, through stimulation of extracellular calcium‐sensing receptors (CaSR), blunt renin production and lead to natriuretic effects in human and experimental cirrhosis. Alongside systemic production, there is Ang II tissue production within various organs through RAS enzymes different from angiotensin‐converting enzyme (ACE), that is chymase, tissue plasminogen activator and several cathepsins. In experimental cirrhosis, inhibition of chymase leads to natriuretic and hepatic antifibrotic effects, without changes in systemic haemodynamics. In the kidney, local RAS coordinates proximal and distal tubular sodium reabsorption. However, renalase, whose plasma and tissue levels are severely altered in experimental cirrhosis, degrades systemic and renal tubule catecholamines, antagonizing the effects of renal RAS. Angiotensinogen‐derived natriuretic and vasodilating peptides (Ang1‐9, Ang1‐7, Ang3‐8) and their receptors have been described. Receptor agonists or antagonists are available to affect portal hypertension and sodium retention in cirrhosis. ACE2‐dependent generation of Ang1‐7 may inhibit experimental liver fibrosis. inhibition of Ang1‐7 clearance by means of neprilysin blockade has portal hypotensive and natriuretic effects. Ang1‐12, whose production renin does not regulate, is converted to several different angiotensin peptides via chymase. Finally, Ang II behaves as either an antinatriuretic or a natriuretic agent, based on the tissue content of AT 1 R and AT 2 R receptors, their ratio being prone to pharmacological modulation.

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Crossref · 10.1111/liv.14272

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Authors
Sansoè, G., Aragno, M., & Wong, F.
Affiliations
  • Division of Gastroenterology Humanitas Gradenigo Hospital Torino Italy
  • University of Turin (IT)
  • University of Toronto (CA)
Venue
Liver International
Publisher
Wiley
Published
2019-11-04
Volume
40
Issue
1
Pages
18-31
ISSN
  • 0106-9543 (ISSN-L)
  • 1478-3223
  • 1478-3231
OpenAlex
W2978207589
Cited by
61
References
128
Citations by year
2026: 4 · 2025: 7 · 2024: 9 · 2023: 13 · 2022: 9 · 2021: 14 · 2020: 5
FWCI
1.27
Type
journal article
Language
en
Open access
Locations
  • Liver International (publishedVersion)
  • PubMed (publishedVersion)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
  • Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Keywords
renin-angiotensin system, liver cirrhosis, chronic liver disease, renal sodium retention, liver fibrosis, chymase, angiotensin II, angiotensin-(1-7), angiotensin-(1-9), renalase, calcium-sensing receptor, neprilysin, angiotensin-converting enzyme 2, angiotensin II type 1 receptor, angiotensin II type 2 receptor, portal hypertension, sodium excretion
MeSH terms
Angiotensin II, Angiotensin-Converting Enzyme Inhibitors, Animals, Chronic Disease, Humans, Kidney Tubules, Proximal, Liver Diseases, Renin-Angiotensin System, Sodium

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