Angiotensin III
Also known as: Ang III, des-Asp-angiotensin II, Angiotensin 2-8, Ang(2-8)
Endogenous heptapeptide; renin-angiotensin system (RAS) metabolite
What it is
Researchers studying blood pressure, kidney function, and the renin-angiotensin system have examined angiotensin III for its role in cardiovascular regulation and brain signalling. It is produced naturally in the body and has emerged as a target for novel antihypertensive drug development, particularly for patients whose blood pressure is difficult to control.
The scientific side
angiotensin III (Ang III) is a biologically active heptapeptide fragment of the renin-angiotensin system (RAS), formed when aminopeptidase A cleaves the N-terminal aspartate residue from angiotensin II (Ang II). Ang III acts primarily through the same AT1 and AT2 angiotensin receptors as Ang II. Binding studies using HEK-293 cells stably transfected with AT1R or AT2R showed that only Ang II and Ang III achieved high affinity at the AT1 receptor, while Ang III also demonstrated substantial AT2 receptor selectivity compared to shorter angiotensin fragments. In vascular smooth muscle cells (VSMCs), Ang III activates ERK1/2 mitogen-activated protein kinases and stimulates DNA synthesis via the AT1 receptor in a concentration- and time-dependent manner; this proliferative signalling was reduced in VSMCs from spontaneously hypertensive rats compared to normotensive Wistar rats. In the brain, Ang III has been identified as a key effector peptide of the central RAS. Research using selective aminopeptidase A inhibitors such as firibastat, which blocks Ang III formation from Ang II in the brain, demonstrated that brain Ang III plays a central role in neurogenic blood pressure regulation and cardiac dysfunction following myocardial infarction; these findings elevated brain aminopeptidase A to a validated therapeutic target (PMIDs: 40694673, 37348757, 34950965). Separately, in vitro exposure of mouse brain endothelial cells (bEnd.3) to Ang III at concentrations between 10 and 1000 nM caused dose- and time-dependent reductions in transendothelial electrical resistance and increases in permeability, accompanied by downregulation of tight junction protein claudin-5 and the lipid transporter Mfsd2a, and upregulation of caveolin-1, indicating disruption of blood-brain barrier integrity through both paracellular and transcellular pathways. In vascular dementia brain tissue, elevated Ang III levels in white matter correlated with ACE-1 activity and small vessel disease severity, suggesting a pathological role for Ang III in cerebral hypoperfusion. Ang III is also a substrate for arginyl-aminopeptidase in the brain, and the activity of this degrading enzyme changes across development and aging, implicating Ang III turnover in CNS maturation.
Class: Endogenous heptapeptide; renin-angiotensin system (RAS) metabolite
Administration & storage
- Administration
- Intravenous infusion (human pharmacological studyPMID 6341391)Cell culture medium addition (in vitro studiesPMIDs 4113659839801458)
- Storage
- No storage conditions for exogenous Ang III preparations were described in the retrieved abstracts. Standard peptide storage conditions (lyophilised at -20°C, protected from moisture and light) would apply generically but are not sourced from the retrieved literature.
Legal & regulatory status
Not approved as a therapeutic drug. Angiotensin III is an endogenous peptide studied as a research tool and pharmacological target. Drug firibastat, which acts by inhibiting brain aminopeptidase A to reduce angiotensin…
Not identified in the fetched literature as a prohibited substance. Angiotensin III is an endogenous peptide; no WADA prohibition status was reported in the retrieved abstracts.
No approved therapeutic product containing angiotensin III identified in the fetched literature.
What it's studied for
- Neurogenic hypertension — brain RAS target Preclinical + Phase 2 clinical (via firibastat)
- Heart failure after myocardial infarction — cardiac dysfunction pathway Preclinical + Phase 2 clinical (via firibastat/QGC606)
- Vascular smooth muscle cell proliferation Preclinical (in vitro, rat cell models)
- Blood-brain barrier disruption under hypertensive conditions Preclinical (in vitro, mouse brain endothelial cells)
- Vascular dementia and cerebral small vessel disease Preclinical (post-mortem human brain tissue analysis)
- Renal and peripheral RAS signalling — endogenous RAAS component Preclinical (animal studies, equilibrium analysis)
- Renal prostaglandin regulation Early human study (pharmacological infusion)
Safety signals
- Blood-brain barrier disruption — endothelial toxicity at nanomolar concentrations
- Vascular smooth muscle cell proliferation — potential vascular remodelling risk
- Elevated Ang III in white matter associated with vascular dementia and small vessel disease pathology
- Cardiac dysfunction and sympathetic overactivation following myocardial infarction — mediated by brain Ang III
- Absence of pressor effect at low doses may mask dose threshold effects — non-linear cardiovascular response
- Reduced circulating Ang III in untreated systemic arterial hypertension (cats) — potential RAAS dysregulation marker
Frequently asked
What is angiotensin III and how is it different from angiotensin II?
Angiotensin III (also called Ang(2-8) or des-Asp-angiotensin II) is a naturally occurring seven-amino-acid peptide formed when an enzyme called aminopeptidase A removes the first amino acid (aspartate) from angiotensin II. Like angiotensin II, it activates AT1 and AT2 receptors and has cardiovascular and blood pressure effects, but research suggests it plays a particularly important role in brain-driven blood pressure regulation. Binding studies confirm only angiotensin II and angiotensin III achieve high affinity at the AT1 receptor among the major angiotensin fragments.
Is there any drug that works by targeting angiotensin III?
Yes — firibastat is an experimental antihypertensive drug that works by inhibiting brain aminopeptidase A, the enzyme that converts angiotensin II into angiotensin III in the brain. By blocking Ang III formation, firibastat reduces neurogenic blood pressure. It has been studied in Phase 2 clinical trials for hypertension and post-myocardial infarction heart failure, though it is not currently approved by the FDA (PMIDs: 40694673, 37348757, 34950965).
Does angiotensin III affect the brain?
Yes. Research identifies brain angiotensin III as a key effector in the central renin-angiotensin system. It activates AT1 receptors in the brain, contributing to sympathetic nervous system activation and blood pressure elevation. It has also been shown in cell culture experiments to disrupt blood-brain barrier integrity at nanomolar concentrations, suggesting a possible role in hypertensive brain injury (PMIDs: 40868980, 41136598, 40694673).
Can angiotensin III levels be measured in the blood?
Yes, angiotensin III can be measured in plasma and serum using methods such as equilibrium analysis and radioimmunoassay. Studies in cats showed circulating Ang III levels of approximately 7.96 pmol/L in healthy controls and 1.56 pmol/L in hypertensive animals. In horses, baseline Ang III was below the limit of detection but rose significantly after furosemide administration (PMIDs: 42117720, 39434560). Accurate measurement requires careful sample handling to prevent peptide degradation.
Is angiotensin III used as a supplement or peptide by the biohacking community?
No evidence of consumer supplement or biohacking use was found in the retrieved scientific literature. Angiotensin III is an endogenous blood pressure peptide studied primarily as a pharmacological target (via drugs like firibastat) rather than as an administered peptide. Its potent cardiovascular effects — including blood pressure elevation via AT1 receptors — would make unsupervised exogenous use potentially hazardous. No protocols for human self-administration exist in the peer-reviewed literature.