Angiotensin 1-7
Also known as: A(1-7), Ang-(1-7), Angiotensin-(1-7), Asp1-Ang-(1-7), AVE0991 (Mas agonist analog), Mas agonist peptide, TXA127
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Summary
Angiotensin‑(1‑7) is a heptapeptide fragment of the renin‑angiotensin system that belongs to the alternative, protective arm of the pathway. It is generated primarily by ACE2‑mediated cleavage of angiotensin II and acts through the Mas receptor to oppose many actions of the classical Ang II‑AT1 axis. Research is exploring its role in blood‑pressure regulation, vascular remodeling, and organ protection, but it remains an investigational compound without approved therapeutic indications.
Mechanism of Action
Angiotensin‑(1‑7) is produced when ACE2 removes the C‑terminal phenylalanine from angiotensin II or directly from angiotensin I. The peptide binds the Mas G‑protein‑coupled receptor, triggering signaling cascades that promote vasodilation, anti‑inflammatory, anti‑fibrotic, and anti‑proliferative effects. Through Mas (and related receptors such as MrgD for alamandine), it counteracts AT1‑mediated vasoconstriction, sodium retention, and tissue remodeling, forming a counter‑regulatory axis within the renin‑angiotensin system.
What the Research Shows
A series of reviews and mechanistic papers describe Ang‑(1‑7) as a key component of the non‑canonical renin‑angiotensin system. Early work highlighted its generation by ACE2 and its capacity to offset angiotensin II’s vasoconstrictive and proliferative actions. Subsequent analyses expanded the concept to an alternative arm that includes Mas, AT2, and MrgD receptors, emphasizing protective cardiovascular, renal, and neural effects. Recent literature underscores the peptide’s potential as a therapeutic target in hypertension, heart failure, and other cardiovascular disorders, while noting that most evidence derives from animal models and biochemical studies rather than large‑scale clinical trials.
Reported Benefits
Evidence from preclinical and translational studies suggests Ang‑(1‑7) can lower vascular resistance, reduce cardiac hypertrophy and fibrosis, and mitigate inflammatory responses. By activating Mas, it promotes nitric‑oxide‑mediated vasodilation and opposes the sodium‑retaining actions of the AT1 pathway, offering a theoretical advantage in conditions characterized by excessive angiotensin II activity.
Limitations of the Evidence
The majority of data are from animal experiments, in‑vitro assays, or review articles; robust human clinical trials are lacking. Consequently, the therapeutic efficacy, optimal dosing, and long‑term outcomes remain uncertain. Its investigational status means no regulatory approvals exist for any indication, and the translational gap between mechanistic findings and clinical application is substantial.
Safety Considerations
Safety information is limited in the cited literature. While vasodilatory actions raise the theoretical risk of hypotension, specific adverse events, tolerability, or toxicity profiles have not been detailed in the available abstracts. Until systematic human studies are conducted, the safety profile of Ang‑(1‑7) remains incompletely characterized.
How It Is Administered
Angiotensin‑(1‑7) has been studied for delivery by inhalation, intravenous infusion, and subcutaneous injection. Formulations are typically peptide solutions suitable for these routes, but precise preparation methods and dosing regimens are not described in the referenced material.
Routes of Administration
Goals & Uses
- COVID-19 / Acute Lung InjuryPulmonary / Infectious DiseaseModerate
- HypertensionCardiovascularModerate
- Anti-cancer / Tumor SuppressionOncologyLow
- Renoprotection / Chronic Kidney DiseaseRenalModerate
- Hematopoietic RecoveryHematologyModerate
- Metabolic / Insulin SensitizationMetabolicLow
- COVID‑19 ARDSRespiratoryLow
- Pulmonary hypertensionCardiovascularModerate
- Cardioprotection / Heart failureCardiovascularModerate
Contraindications
- PregnancyPopulationModeratePotential fetal risk or insufficient safety data
- Hypersensitivity to Angiotensin 1-7 or excipientsAllergy / ImmunologicHigh
- Severe hypotensionCardiovascularHigh
Adverse Effects
- Injection site reactionsLocalCommon
- HeadacheNeurologicUnknownPain in the head or upper neck
- HypotensionCardiovascularUnknownLow blood pressure
- FlushingVascularUncommonWarmth and redness of the skin
- DizzinessNeurologicUnknownFeeling faint, lightheaded, or unsteady
- BradycardiaCardiovascularRare
Drug Interactions
- Antihypertensive agentsModerate
- Angiotensin Receptor Blockers (ARBs)Low
- Angiotensin II Receptor Blockers (ARBs, e.g., losartan)Moderate
- NSAIDsLowMay increase renal risk in susceptible patients
- ACE inhibitorsModerate
- ACE Inhibitors (e.g., enalapril, lisinopril)Moderate
Population Constraints
- Patients with baseline hypotensionCardiovascularRelative
- Severe renal impairmentOrgan ImpairmentRelative
- Pediatric patientsAgeRelative
- ElderlyAgeRelative
- Pregnant womenReproductiveRelative
- ChildrenPediatricRelative
Regulatory Status
- European UnionInvestigationalClinical studies ongoing.
- United StatesInvestigationalUnder IND for cardiovascular trials.
- United KingdomInvestigationalBeing evaluated in Phase 2 studies.
Not approved for clinical use in any jurisdiction; currently studied in Phase 1‑2 clinical trials.
Evidence & Sources
- Journal ArticleModerateTe Riet L, et al.2015-01-01T00:00:00.000000Z
- Journal ArticleModerateSantos RA2014-01-01T00:00:00.000000Z
- Journal ArticleModerateSantos RA, Campagnole-Santos MJ, Andrade SP2000-01-01T00:00:00.000000Z
- Journal ArticleModerateBader M, et al.2024-01-01T00:00:00.000000Z
- Journal ArticleModeratePaz Ocaranza M, et al.2020-01-01T00:00:00.000000Z
- Journal ArticleModerateSantos RAS, et al.2018-01-01T00:00:00.000000Z
Frequently Asked Questions
What distinguishes Angiotensin‑(1‑7) from traditional RAAS blockers?
Traditional blockers inhibit enzymes or receptors that generate or respond to angiotensin II, whereas Ang‑(1‑7) is a downstream peptide that actively signals through the Mas receptor to produce opposite, protective effects, rather than merely blocking a pathway.
Is Angiotensin‑(1‑7) currently approved for any medical use?
No. All cited sources describe Ang‑(1‑7) as investigational and research‑only; it has not received regulatory approval for therapeutic use in any indication.
What potential clinical conditions could benefit from Ang‑(1‑7) therapy?
Preclinical data suggest possible benefits in hypertension, cardiac hypertrophy, fibrosis, and other cardiovascular diseases where excessive angiotensin II activity contributes to pathology, but human evidence is still lacking.
How is Angiotensin‑(1‑7) administered in experimental settings?
Studies have employed inhalation, intravenous, and subcutaneous routes using peptide solutions, reflecting its peptide nature and the need for systemic or pulmonary delivery to reach target tissues.
What are the main safety concerns with Ang‑(1‑7)?
The literature does not report specific adverse events; however, its vasodilatory action could theoretically cause low blood pressure, and comprehensive safety data are not yet available.
What is Angiotensin 1-7?
Angiotensin‑(1‑7) is a heptapeptide fragment of the renin‑angiotensin system that belongs to the alternative, protective arm of the pathway. It is generated primarily by ACE2‑mediated cleavage of angiotensin II and acts through the Mas receptor to oppose many actions of the classical Ang II‑AT1 axis. Research is exploring its role in blood‑pressure regulation, vascular remodeling, and organ protection, but it remains an investigational compound without approved therapeutic indications.
What is Angiotensin 1-7 used for?
Angiotensin 1-7 is educationally associated with: COVID-19 / Acute Lung Injury, Hypertension, Anti-cancer / Tumor Suppression, Renoprotection / Chronic Kidney Disease, Hematopoietic Recovery, Metabolic / Insulin Sensitization, COVID‑19 ARDS, Pulmonary hypertension, Cardioprotection / Heart failure. Educational only — not medical advice.
How is Angiotensin 1-7 administered?
Recorded routes of administration: Inhalation, Intravenous, Subcutaneous.
What are the potential side effects of Angiotensin 1-7?
Reported adverse effects include: Injection site reactions, Headache, Hypotension, Flushing, Dizziness, Bradycardia. This list is not exhaustive — consult a qualified clinician.
Who should avoid Angiotensin 1-7?
Recorded contraindications: Pregnancy, Hypersensitivity to Angiotensin 1-7 or excipients, Severe hypotension. Consult a qualified clinician before use.