New Components of the Renin-Angiotensin System: Alamandine and the Mas-Related G Protein-Coupled Receptor D

  • Gisele Maia Etelvino
  • Antônio Augusto Bastos Peluso
  • Robson Augusto Souza SantosEmail author
Hypertension and the Kidney (R Carey, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Hypertension and the Kidney


The renin-angiotensin system is an important component of the central and humoral mechanisms of blood pressure and hydro-electrolytic balance control. Angiotensin II is a key player of this system. Twenty-five years ago the first manuscripts describing the formation and actions of another peptide of the RAS, angiotensin-(1-7), were published. Since then several publications have shown that angiotensin-(1-7) is as pleiotropic as angiotensin II, influencing the functions of many organs and systems. The identification of the ACE homologue ACE2 and, a few years later, Mas, as a receptor for angiotensin-(1-7) contributed a great deal to establish this peptide as a key player of the RAS. Most of the actions of angiotensin-(1-7) are opposite to those described for angiotensin II. This has led to the concept of two arms of the RAS: one comprising ACE/AngII/AT1R and the other ACE2/Ang-(1-7)/Mas. More recently, we have described the identification of a novel component of the RAS, alamandine, which binds to the Mas-related G protein coupled receptor D. This peptide is formed by decarboxylation of the Asp residue of angiotensin-(1-7), leading to the formation of Ala as the N-terminal amino acid. Alternatively, it can be formed by hydrolysis of Ang A, by ACE2. Its effects include vasorelaxation, central effects similar to those produced by angiotensin-(1-7), blunting of isoproterenol-induced heart fibrosis, and anti-hypertensive action in SHR. The putative enzyme responsible for alamandine formation from angiotensin-(1-7) is under investigation. The identification of this novel component of the RAS opens new venues for understanding its physiological role and opens new putative therapeutic possibilities for treating cardiovascular diseases.


Mas1 Angiotensin II Angiotensin-(1-7) Hypertension Angiotensin-(1-12) Angiotensin A 



This work was supported by Conselho Nacional de Pesquisas (CNPq), Fundação de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).

Compliance with Ethics Guidelines

Conflict of Interest

Gisele Maia Etelvino, Antônio Augusto Bastos Peluso, and Robson Augusto Souza Santos declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Gisele Maia Etelvino
    • 1
  • Antônio Augusto Bastos Peluso
    • 1
  • Robson Augusto Souza Santos
    • 1
    Email author
  1. 1.National Institute of Science and Technology in Nanobiopharmaceutics, Department of Physiology and BiophysicsFederal University of Minas GeraisBelo HorizonteBrazil

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