ACE inhibition, ACE2 and angiotensin-(1-7) axis in kidney and cardiac inflammation and fibrosis

Pharmacol Res. 2016 May;107:154-162. doi: 10.1016/j.phrs.2016.03.018. Epub 2016 Mar 17.


The Renin Angiotensin System (RAS) is a pivotal physiological regulator of heart and kidney homeostasis, but also plays an important role in the pathophysiology of heart and kidney diseases. Recently, new components of the RAS have been discovered, including angiotensin converting enzyme 2 (ACE2), Angiotensin(Ang)-(1-7), Mas receptor, Ang-(1-9) and Alamandine. These new components of RAS are formed by the hydrolysis of Ang I and Ang II and, in general, counteract the effects of Ang II. In experimental models of heart and renal diseases, Ang-(1-7), Ang-(1-9) and Alamandine produced vasodilation, inhibition of cell growth, anti-thrombotic, anti-inflammatory and anti-fibrotic effects. Recent pharmacological strategies have been proposed to potentiate the effects or to enhance the formation of Ang-(1-7) and Ang-(1-9), including ACE2 activators, Ang-(1-7) in hydroxypropyl β-cyclodextrin, cyclized form of Ang-(1-7) and nonpeptide synthetic Mas receptor agonists. Here, we review the role and effects of ACE2, ACE2 activators, Ang-(1-7) and synthetic Mas receptor agonists in the control of inflammation and fibrosis in cardiovascular and renal diseases and as counter-regulators of the ACE-Ang II-AT1 axis. We briefly comment on the therapeutic potential of the novel members of RAS, Ang-(1-9) and alamandine, and the interactions between classical RAS inhibitors and new players in heart and kidney diseases.

Keywords: Alamandine; Angiotensin converting enzyme 2; Angiotensin-(1-7); Angiotensin-(1-9); Mas receptor; Renin angiotensin system.

Publication types

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

MeSH terms

  • Angiotensin I / agonists
  • Angiotensin I / metabolism*
  • Angiotensin-Converting Enzyme 2
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Animals
  • Heart Diseases / metabolism*
  • Humans
  • Kidney Diseases / metabolism*
  • Oligopeptides / metabolism
  • Peptide Fragments / agonists
  • Peptide Fragments / metabolism*
  • Peptidyl-Dipeptidase A / metabolism*
  • Proto-Oncogene Proteins / metabolism
  • Receptors, G-Protein-Coupled / metabolism


  • Angiotensin-Converting Enzyme Inhibitors
  • Oligopeptides
  • Peptide Fragments
  • Proto-Oncogene Proteins
  • Receptors, G-Protein-Coupled
  • alamandine
  • angiotensin I (1-9)
  • proto-oncogene proteins c-mas-1
  • Angiotensin I
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • angiotensin I (1-7)