Angiotensin-(1-7) in kidney disease: a review of the controversies

Clin Sci (Lond). 2012 Sep;123(6):333-46. doi: 10.1042/CS20120111.

Abstract

Ang-(1-7) [angiotensin-(1-7)] is a biologically active heptapeptide component of the RAS (renin-angiotensin system), and is generated in the kidney at relatively high levels, via enzymatic pathways that include ACE2 (angiotensin-converting enzyme 2). The biological effects of Ang-(1-7) in the kidney are primarily mediated by interaction with the G-protein-coupled receptor Mas. However, other complex effects have been described that may involve receptor-receptor interactions with AT(1) (angiotensin II type 1) or AT(2) (angiotensin II type 2) receptors, as well as nuclear receptor binding. In the renal vasculature, Ang-(1-7) has vasodilatory properties and it opposes growth-stimulatory signalling in tubular epithelial cells. In several kidney diseases, including hypertensive and diabetic nephropathy, glomerulonephritis, tubulointerstitial fibrosis, pre-eclampsia and acute kidney injury, a growing body of evidence supports a role for endogenous or exogenous Ang-(1-7) as an antagonist of signalling mediated by AT(1) receptors and thereby as a protector against nephron injury. In certain experimental conditions, Ang-(1-7) appears to paradoxically exacerbate renal injury, suggesting that dose or route of administration, state of activation of the local RAS, cell-specific signalling or non-Mas receptor-mediated pathways may contribute to the deleterious responses. Although Ang-(1-7) has promise as a potential therapeutic agent in humans with kidney disease, further studies are required to delineate its signalling mechanisms in the kidney under physiological and pathophysiological conditions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiotensin I / genetics
  • Angiotensin I / pharmacology
  • Angiotensin I / physiology*
  • Angiotensin-Converting Enzyme 2
  • Animals
  • Diabetic Nephropathies / metabolism
  • Humans
  • Kidney Diseases / genetics
  • Kidney Diseases / metabolism*
  • Mice
  • Peptide Fragments / genetics
  • Peptide Fragments / pharmacology
  • Peptide Fragments / physiology*
  • Peptidyl-Dipeptidase A / genetics
  • Peptidyl-Dipeptidase A / physiology
  • Proto-Oncogene Proteins / metabolism
  • Rats
  • Receptor, Angiotensin, Type 1 / metabolism
  • Receptor, Angiotensin, Type 1 / physiology
  • Receptors, G-Protein-Coupled / metabolism
  • Signal Transduction

Substances

  • Peptide Fragments
  • Proto-Oncogene Proteins
  • Receptor, Angiotensin, Type 1
  • Receptors, G-Protein-Coupled
  • proto-oncogene proteins c-mas-1
  • Angiotensin I
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Ace2 protein, mouse
  • Ace2 protein, rat
  • Angiotensin-Converting Enzyme 2
  • angiotensin I (1-7)