The renin-angiotensin system: going beyond the classical paradigms

Area of Science:

• Physiology
• Cardiovascular Research
• Endocrinology

Background:

• The renin-angiotensin system (RAS) has a newly discovered axis involving angiotensin-(1-7) [ANG-(1-7)], mediated by angiotensin-converting enzyme 2 (ACE2) and the Mas receptor.
• The ANG-(1-7)/ACE2/Mas axis and the angiotensin II type 2 receptor (AT₂R) exhibit protective cardiovascular effects, contrasting with the detrimental actions of the angiotensin II type 1 receptor (AT₁R).
• A novel RAS branch involves alatensins, such as alamandine (Ala-ANG-(1-7)), which interact with Mas-related G protein-coupled receptor D and show protective cardiovascular effects.

Purpose of the Study:

• To review the signaling and physiological actions of ANG-(1-7), ACE2, AT₂R, and alatensins, focusing on non-central nervous system tissues.
• To discuss the therapeutic opportunities presented by these newly understood RAS pathways.
• To summarize findings presented at the 2017 International Union of Physiological Sciences Congress symposium on 'The Renin-Angiotensin System: Going Beyond the Classical Paradigms.'

Main Methods:

• Review of presentations from a 2017 symposium.
• Synthesis of existing research on ANG-(1-7), ACE2, AT₂R, and alatensins.
• Focus on functional analysis and physiological actions in cardiovascular systems.

Main Results:

• The ANG-(1-7)/ACE2/Mas axis demonstrates significant protective roles in cardiovascular diseases.
• AT₂R activation also confers cardiovascular protection, while AT₁R activation is associated with adverse effects.
• Alatensins, like alamandine, represent a new RAS branch with demonstrated protective cardiovascular functions.

Conclusions:

• The RAS comprises multiple axes with distinct, often opposing, physiological roles.
• The ANG-(1-7)/ACE2/Mas pathway and alatensins offer promising therapeutic targets for cardiovascular diseases.
• Further research into these non-classical RAS pathways can unlock novel treatment strategies for cardiovascular conditions.