Angiotensin 1-7

Angiotensin 1-7 is an endogenous heptapeptide produced from angiotensin II by angiotensin-converting enzyme 2 (ACE2). It functions as the primary agonist of the Mas receptor, a G-protein-coupled receptor whose activation counterbalances the vasoconstricting, pro-inflammatory, and pro-fibrotic actions of the classical renin-angiotensin system (RAS). Ang-(1-7) is central to the counter-regulatory RAS axis and gained significant research attention during COVID-19 due to its protective role in the lungs.

Angiotensin 1-7 binds the Mas receptor to activate downstream signaling that opposes angiotensin II effects. Mas receptor activation promotes vasodilation through nitric oxide release, reduces inflammation by suppressing NF-κB-mediated cytokine production, and limits fibrosis by inhibiting TGF-β signaling. In pulmonary physiology, the ACE2/Ang-(1-7)/Mas axis protects alveolar epithelium from acute lung injury. SARS-CoV-2 infection downregulates ACE2 expression, impairing Ang-(1-7) production and disrupting this protective axis — a mechanism implicated in severe COVID-19 lung pathology.

Preclinical research demonstrates organ-protective effects in rodent models of hypertension, heart failure, and acute lung injury. During COVID-19, multiple Phase 1-2 trials investigated Ang-(1-7) infusion in ICU patients; a 2024 trial published in Annals of Intensive Care showed safety and preliminary efficacy signals. Several synthetic Mas receptor agonist analogs (AVE 0991, cyclic Ang-(1-7)) have shown protective effects preclinically but remain unapproved. Research is active as of 2026.