Angiotensin (1-7)

Angiotensin (1-7) is generated mainly by ACE2 cleaving angiotensin II, and it signals through the G-protein-coupled Mas receptor. Mas activation raises endothelial nitric oxide and prostaglandin output, producing vasodilatation and antithrombotic effects, and it suppresses NADPH oxidase, TGF-beta and NF-kB signalling, which is the basis of its antifibrotic and anti-inflammatory reputation. It also mobilises haematopoietic and mesenchymal progenitors, which is why the TXA127 programme targeted chemotherapy-induced cytopenias and wound repair. Native Ang-(1-7) is degraded within minutes by ACE and aminopeptidases, so the pharmaceutical versions use modifications such as the NorLeu3 substitution to slow breakdown. Almost all of the cardiac and renal protection claims rest on animal work.

Targets: Mas receptor (MAS1), Nitric oxide / eNOS pathway, TGF-beta and NF-kB signalling, ACE2 axis

• · Trial dosing was weight-based, in the region of 100 mcg/kg per day, rather than a fixed milligram amount. No consumer protocol has been validated and the research-chemical market has no standard.
• · Used a NorLeu3-A(1-7) gel for diabetic foot ulcers. This programme did not reach approval.

Work out your exact syringe units →

• commonInjection-site reaction
• uncommonHypotension or lightheadedness— Vasodilatory by mechanism, though far weaker than angiotensin II is pressor.
• uncommonHeadache
• rareTheoretical proliferative effects from progenitor mobilisation— Not documented in humans, but it is the mechanistic reason to be careful in active cancer.

• Active malignancy - the peptide mobilises progenitor cells and its effect on tumour biology in humans is unknown.
• Symptomatic hypotension or concurrent aggressive antihypertensive therapy.
• Pregnancy, where no safety data exist for any RAS-modulating peptide.

• synergyACE inhibitors — ACE inhibition blocks the degradation of Ang-(1-7) and raises endogenous levels, amplifying both the effect and the blood pressure drop.
• synergyangiotensin receptor blockers — ARBs shunt angiotensin II toward the ACE2/Ang-(1-7) pathway, which is mechanistically complementary.
• synergybpc-157 — Commonly stacked in repair protocols on the theory of shared nitric-oxide and angiogenic signalling; this pairing is entirely anecdotal.

• · Blood pressure, particularly in anyone already on RAS-blocking medication.
• · Complete blood count if using it for haematopoietic support, which is where the human data actually sit.
• · Objective tracking of whatever the target problem is - wound size, function, symptom scores.

Not approved for human use anywhere. Sold as a research chemical; the pharmaceutical versions remain investigational.

• Rodgers et al., NorLeu3-A(1-7) in diabetic foot ulcer healing (trial)
• Santos et al., the ACE2/angiotensin-(1-7)/Mas axis review (review)
• Pham et al., angiotensin-(1-7) and haematopoietic recovery after chemotherapy (preclinical)

Angiotensin-(1-7) is the output of the protective arm of the renin-angiotensin system. ACE2 cleaves the C-terminal phenylalanine from angiotensin II to make it, and it then signals through Mas, a G protein-coupled receptor that is structurally unrelated to AT1 and AT2. Mas activation raises nitric oxide and prostaglandin production through Akt-dependent eNOS phosphorylation, opposes NADPH oxidase-driven reactive oxygen species generation, and suppresses the MAP kinase and TGF-beta signalling that drives fibroblast proliferation and collagen deposition. The net effect is a mirror image of AT1 signalling: vasodilation instead of vasoconstriction, antifibrotic instead of profibrotic, anti-inflammatory instead of pro-inflammatory, and antiproliferative in vascular smooth muscle. There is also a distinct haematopoietic effect that has nothing to do with blood pressure: Mas receptors on bone marrow progenitors, and angiotensin-(1-7) accelerates recovery of platelets and neutrophils after chemotherapy or radiation, which is what the TXA127 clinical programme was actually about. The wound healing effect studied with NorLeu3-A(1-7) appears to run through increased progenitor cell recruitment and angiogenesis in the wound bed. The gap between that mechanism and what people buy angiotensin-(1-7) for is large: the cardiovascular, antifibrotic and longevity claims are essentially all rodent work, and the human data that exist are in chemotherapy-induced cytopenias and diabetic foot ulcers.

The main thing that goes wrong is a category error. This is a peptide with genuine, well-characterised receptor pharmacology, a serious basic-science literature, and human trials in two narrow indications, being sold and used for cardiovascular protection, antifibrotic effects and longevity on the strength of rodent studies. The native peptide's 10 to 30 minute half-life means that subcutaneous injection once or twice daily produces brief spikes and long troughs, and nobody has shown that this dosing pattern reproduces anything from the infusion studies. There is no quality-controlled human product; what is sold is research-chemical grade with unverified identity. And because it is a vasodilator that stacks on top of whatever antihypertensives someone is already taking, symptomatic hypotension is the realistic acute problem.

• Mas receptor (MAS1)

  The principal receptor. NO and prostaglandin release, eNOS activation via Akt, suppression of NADPH oxidase, TGF-beta and MAP kinase signalling. Produces vasodilation, antifibrotic and anti-inflammatory effects.

• AT2 receptor

  A secondary contributor to the vasodilatory and antiproliferative effects; some angiotensin-(1-7) actions are blocked by AT2 antagonists as well as by the Mas antagonist A-779.

• AT1 receptor

  Weak antagonism or functional opposition at high concentrations; not the main mechanism.

• NorLeu3-A(1-7) (DSC127) phase 2 diabetic foot ulcer trial Phase 2 · n=77 · 24 weeks · 2012

  Percentage of ulcers completely epithelialised at week 12 after 4 weeks of once-daily topical gel. Dose-response on area reduction, and median time to healing 8.5 weeks with 0.03 percent DSC127 versus 22 weeks with placebo (p=0.04). 172 patients were screened; 77 were randomised across three arms.

• Angiotensin-(1-7) in recurrent ovarian cancer patients receiving gemcitabine and platinum chemotherapy Phase 1/2 · 2013

  Pharmacodynamic stimulation of thrombogenesis, that is, platelet recovery, during myelosuppressive chemotherapy. Signal present; no approval followed.

Vascular effects are immediate during infusion and gone within an hour of stopping. In the topical wound trials, separation from placebo on area reduction appeared over weeks, with median complete healing at 8.5 weeks versus 22 weeks. Haematopoietic effects were measured over chemotherapy cycles, that is, weeks.

ACE inhibitors are the natural partner in the sense that they raise endogenous angiotensin-(1-7) and slow its breakdown, so the combination is mechanistically coherent and additively hypotensive. ARBs shunt angiotensin II toward ACE2 and also raise angiotensin-(1-7), same logic. Combining it with other vasodilators or with high-dose nitric oxide precursors compounds the blood pressure effect. There is no evidence base for the stacks it is usually sold in, which typically pair it with BPC-157, TB-500 or growth hormone secretagogues on the strength of shared rodent wound-healing literature.

Against angiotensin II, its precursor: functional opposites through different receptors, and one is made from the other by ACE2. Against ACE inhibitors and ARBs, which raise endogenous angiotensin-(1-7) as part of how they work: those drugs have decades of hard outcome data and are the rational way to engage this axis in anyone with cardiovascular disease. Against the other regenerative peptides it is usually stacked with, angiotensin-(1-7) actually has a randomised, placebo-controlled human wound healing trial, which puts it ahead of BPC-157 on evidence even though it is far less popular.

No approved human product. Research-chemical vials are widely listed but I did not verify current pricing, and the price of an unverified product is not a useful number.

• ?Half-life figures of 10 to 30 minutes are widely cited but I did not resolve a primary human pharmacokinetic study in this session; volume of distribution, clearance and protein binding are all null.
• ?Blood-brain barrier penetration is marked partial on the basis of central Mas receptor effects reported in animal work; I did not verify human CNS penetration.
• ?The participant count for the ovarian cancer chemotherapy study was not resolved and is left null.
• ?Whether the NorLeu3 topical result would translate to any systemic use is entirely unestablished; the trial tested a gel on a wound bed.

• NorLeu3-A(1-7) stimulation of diabetic foot ulcer healing: results of a randomized, parallel-group, double-blind, placebo-controlled phase 2 clinical trial Balingit PP, Armstrong DG, Reyzelman AM, et al., Wound Repair Regen, 2012 · PMID 22672145

  The single best-controlled human trial of an angiotensin-(1-7) analogue, and it is topical, not systemic.

• Pharmacodynamic stimulation of thrombogenesis by angiotensin (1-7) in recurrent ovarian cancer patients receiving gemcitabine and platinum-based chemotherapy Pham H, Schwartz BM, Delmore JE, et al., Cancer Chemother Pharmacol, 2013 · PMID 23370663

  The human haematopoietic recovery data, which is the most concrete clinical signal the native peptide has.

• Angiotensin 1-7 stimulation of platelet recovery Rodgers KE, diZerega GS, Expert Opin Investig Drugs, 2014 · PMID 24555825

  Review of the haematopoietic programme by the group that ran it.

• Alternative renin-angiotensin system Bader M, Ferrario CM, et al., Hypertension, 2024 · PMID 38362781

  Current authoritative review of the ACE2 / angiotensin-(1-7) / Mas axis.

• Acceleration of healing, reduction of fibrotic scar, and normalization of tissue architecture by an angiotensin analogue, NorLeu3-A(1-7) Rodgers KE, Roda N, Felix JE, et al., Plast Reconstr Surg, 2003 · PMID 12621191

  The preclinical wound healing work that the DSC127 programme was built on.