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phase 2Cardiovascular

Angiotensin-(1-7)

Also known as: Ang-(1-7), Angiotensin 1-7, Ang1-7, Counter-regulatory Angiotensin

Angiotensin-(1-7) is a seven-amino acid endogenous peptide of the renin-angiotensin system (RAS) that acts as the physiological counterbalance to angiotensin II. Formed primarily by the action of ACE2 on angiotensin II, Ang-(1-7) activates the Mas receptor to produce vasodilation, anti-inflammatory, anti-fibrotic, and cardioprotective effects. It represents a key component of the protective arm of the RAS and has gained significant research attention since the COVID-19 pandemic highlighted the importance of ACE2 biology.

4 cited references·6 researched benefits

Quick Answer

Angiotensin-(1-7) is a seven-amino acid peptide in the renin-angiotensin system that counteracts the harmful effects of angiotensin II. Produced by ACE2 enzyme activity, it activates the Mas receptor to produce vasodilation, reduce inflammation, prevent fibrosis, and protect the heart. Phase 2 clinical trials are exploring its potential for treating heart failure, pulmonary hypertension, and cardiovascular protection.

Key Facts

Mechanism
Angiotensin-(1-7) is generated primarily by ACE2-mediated cleavage of angiotensin II, removing the C-terminal phenylalanine residue. It can also be formed by neprilysin or prolyl endopeptidase acting on angiotensin I. Ang-(1-7) binds and activates the Mas receptor (MasR), a G-protein-coupled receptor, triggering signaling cascades that include: nitric oxide (NO) and prostacyclin release causing vasodilation; inhibition of MAPK/ERK pathways reducing cell proliferation; suppression of NF-κB and pro-inflammatory cytokines; reduction of TGF-β signaling to inhibit fibrosis; and enhanced bradykinin activity. Ang-(1-7) is degraded by ACE and dipeptidyl peptidase 3 (DPP3).
Research Status
phase 2
Half-Life
~10-15 seconds (endogenous); ~30 minutes (cyclodextrin-formulated)
Molecular Formula
C₄₁H₆₂N₁₂O₁₁
Primary Use
Cardiovascular
Table of Contents

Benefits

  • Vasodilation and blood pressure reduction through Mas receptor activation and nitric oxide releasestrong
  • Anti-fibrotic effects — reduces cardiac, pulmonary, and renal fibrosis in animal modelsmoderate
  • Anti-inflammatory properties — suppresses NF-κB and pro-inflammatory cytokine productionmoderate
  • Cardioprotection — reduces infarct size and improves post-ischemic recovery in preclinical modelsmoderate
  • Anti-thrombotic effects — inhibits platelet aggregation and thrombus formationpreliminary
  • Renal protection — preserves glomerular filtration and reduces proteinuria in disease modelsmoderate

Dosage Protocols

RouteDosage RangeFrequencyNotes
Intravenous infusion (investigational)0.03-0.3 mcg/kg/minContinuous infusion for study durationVery short endogenous half-life (~10-15 seconds) necessitates continuous infusion or stabilized formulations.
Subcutaneous injection (investigational — cyclodextrin formulation)50-500 mcg/kgOnce or twice dailyHydroxypropyl-β-cyclodextrin (HPβCD) inclusion complex extends effective half-life to approximately 30 minutes. TXA127 is an investigational formulation under clinical development.
Oral (investigational)Under developmentNot establishedOral formulations using cyclodextrin encapsulation are in early clinical development to overcome rapid proteolytic degradation.

Medical disclaimer

Dosage information is provided for educational reference only. Always follow your prescriber's instructions and consult a qualified healthcare provider before starting any peptide protocol.

Side Effects

  • Hypotension, particularly with concurrent antihypertensive therapycommon
  • Injection site reactions (subcutaneous formulations)common
  • Dizziness and lightheadedness from blood pressure reductioncommon
  • Flushingrare
  • Severe hypotension requiring intervention in susceptible individualsserious

Frequently Asked Questions

What is the relationship between angiotensin-(1-7) and ACE2?
ACE2 (angiotensin-converting enzyme 2) is the primary enzyme that produces angiotensin-(1-7) by cleaving the last amino acid from angiotensin II. This converts the potent vasoconstrictor angiotensin II into the vasodilatory, anti-inflammatory Ang-(1-7). ACE2 gained global attention as the cell entry receptor for SARS-CoV-2, and COVID-19 was found to downregulate ACE2, potentially reducing protective Ang-(1-7) levels and contributing to the severe cardiovascular and pulmonary inflammation seen in the disease.
How does angiotensin-(1-7) differ from angiotensin II?
Angiotensin II and angiotensin-(1-7) have essentially opposite effects. Angiotensin II binds AT1 receptors to cause vasoconstriction, inflammation, fibrosis, oxidative stress, and sodium retention. Angiotensin-(1-7) binds Mas receptors to produce vasodilation, anti-inflammation, anti-fibrosis, antioxidant effects, and natriuresis. They represent the two opposing arms of the renin-angiotensin system. ACE2 converts the harmful angiotensin II into the protective Ang-(1-7), making ACE2 a critical regulator of this balance.
What clinical trials are studying angiotensin-(1-7)?
Several phase 1 and phase 2 clinical trials have studied Ang-(1-7) or its analogs. TXA127 (a formulated version) has been investigated for prevention of graft-versus-host disease after stem cell transplant and for reducing pulmonary fibrosis. Trials have explored its use in heart failure with preserved ejection fraction (HFpEF), COVID-19-related lung injury, and diabetic kidney disease. The short half-life remains the main barrier to clinical translation, driving development of stabilized analogs and delivery systems.
Can angiotensin-(1-7) be taken as a supplement?
Angiotensin-(1-7) is not available as a dietary supplement and cannot be taken orally in its native form due to immediate degradation by gastrointestinal proteases. It is an investigational peptide studied in controlled clinical trials via intravenous or subcutaneous administration using specialized formulations. There is no FDA-approved form for consumer use. Individuals interested in supporting their endogenous Ang-(1-7) levels may benefit from ACE inhibitors or ARBs (which shift RAS balance) and regular exercise, both of which increase Ang-(1-7) production.

References

  1. 1
    Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas(2003)PubMed ↗
  2. 2
    The ACE2/angiotensin-(1-7)/Mas axis: therapeutic target in cardiovascular disease(2015)PubMed ↗
  3. 3
    Angiotensin-(1-7): cardioprotective effect in myocardial ischemia/reperfusion(2008)PubMed ↗
  4. 4
    ACE2, angiotensin-(1-7), and Mas receptor axis in inflammation and fibrosis(2014)PubMed ↗

Latest Research

Last updated: 2026-02-19