Angiotensin II

Giapreza, synthetic human angiotensin II acetate, LJPC-501, Ang II, Hypertensin (historical)

Cardiovascular & circulation

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Note on this profile. Synthetic angiotensin II is an approved intensive-care medicine in the US (2017) and EU (2019), given by continuous intravenous infusion to patients in shock. It is not a research-only compound and has no outpatient or self-directed use. This page explains the published science.

1What it is

Angiotensin II is the body's own pressor hormone — the end product of the renin–angiotensin cascade that the kidneys trigger when blood pressure falls. Most people encounter it indirectly, as the thing ACE inhibitors and "sartans" block to treat hypertension. The drug is the identical peptide, synthesised and given by infusion to do the opposite: raise blood pressure in distributive (vasodilatory) shock — most often septic shock — when fluids and catecholamines such as noradrenaline are not enough. Bovine-derived angiotensin preparations were used as pressors in the 1960s and faded out; the modern synthetic human product was developed by a small US company and approved by the FDA in December 2017 after the ATHOS-3 trial, with EU approval following in 2019. It was the first new class of vasopressor in decades.

It has no community use. It is one of the very few peptides on this site where a dose error could be fatal within minutes, which is why it is given only through a central line in intensive care with continuous arterial monitoring.

2How it's thought to work

AT1 receptor. stimulation on arteriolar smooth muscle causes rapid, powerful vasoconstriction through a mechanism independent of the adrenergic receptors that catecholamines use — the rationale for adding it when noradrenaline is failing ("multimodal" vasopressor therapy).

Adrenal cortex. releases aldosterone, promoting sodium and water retention.

Pituitary and sympathetic system. stimulates vasopressin release and noradrenaline release from nerve endings.

Kidney. constricts the efferent arteriole, which can preserve glomerular filtration pressure; post hoc analyses suggested better renal recovery in patients on renal replacement therapy.

In sepsis the enzyme ACE may be deficient or inhibited, lowering endogenous angiotensin II and raising angiotensin I and renin; patients with high renin appear to respond best, which is the basis of ongoing "renin-guided" research.

Angiotensin II at the AT1 receptor on vascular smooth muscle. The muscle contracts and the lumen narrows, raising blood pressure; a second arm acts on the adrenal cortex to release aldosterone, which holds on to sodium and water.Schematic — not to scale

3What the research shows

Vasodilatory shock (ATHOS-3)

A double-blind, placebo-controlled phase 3 trial randomised 344 adults with catecholamine-resistant vasodilatory shock (requiring >0.2 µg/kg/min noradrenaline-equivalent) to angiotensin II or placebo on top of standard vasopressors. The primary endpoint — mean arterial pressure ≥75 mmHg or a ≥10 mmHg rise at 3 hours without increasing background vasopressors — was met by 69.9% vs 23.4%. Background vasopressor doses fell. All-cause mortality at 28 days was 46% vs 54%, not statistically significant (Khanna 2017, NEJM). The trial was powered for blood pressure, not survival. [1]

Post hoc analyses

In ATHOS-3 patients on renal replacement therapy, those given angiotensin II had higher 28-day survival and more liberation from dialysis (Tumlin 2018, Crit Care Med). Patients with high renin had higher mortality and appeared to benefit more from angiotensin II (Bellomo 2020, Am J Respir Crit Care Med). These generate hypotheses rather than prove benefit. [2][3]

Observational and real-world series

Single- and multi-centre cohorts since 2018 report MAP response in roughly half to two-thirds of patients, with mortality that tracks the severity of illness (Wieruszewski 2021, Crit Care †). Early initiation and lower background vasopressor dose predict response.

Graded B/C

Cardiac surgery vasoplegia, liver transplantation, ACE-inhibitor overdose

Case series and small studies describe use for post-bypass vasoplegia and for hypotension during liver transplantation; a physiological rationale exists for ACE-inhibitor poisoning. None is a licensed indication.

Not gradednot established

Comparative effectiveness versus vasopressin

No head-to-head has compared angiotensin II with vasopressin as the second-line agent; guidelines (Surviving Sepsis Campaign 2021) do not recommend it over vasopressin because of limited data and cost.

4Reported side effects and interactions

Literature-reported

thromboembolic events were the signal in ATHOS-3 — 12.9% vs 5.1% (deep-vein thrombosis the most frequent), and the label advises concurrent venous thromboprophylaxis; also tachycardia, thrombocytopenia, delirium, acidosis, peripheral ischaemia, fungal infection, hyperglycaemia. Excessive vasoconstriction can cause digital, mesenteric or myocardial ischaemia, as with any potent pressor. Rebound hypotension if stopped abruptly.

Community-reported

essentially none documented.

Theoretical. prolonged exposure to angiotensin II promotes fibrosis, inflammation and oxidative stress in animal models; relevance to infusions lasting hours to days is unknown.

Interactions. ACE inhibitors increase and prolong the response (ACE no longer needed to generate drug, and degradation pathways shift); angiotensin receptor blockers reduce it; additive effects with other vasopressors and inotropes.

Markers researchers commonly monitor

Taken from the label and intensive-care practice:

Marker	Why it's watched
Continuous arterial blood pressure (MAP)	the titration target; the drug acts within minutes.
Background vasopressor dose (noradrenaline-equivalent)	a falling requirement is the practical measure of effect.
Lactate, central venous oxygen saturation, urine output	perfusion adequacy, not just pressure.
Limb and skin perfusion, ECG, troponin	ischaemic complications of excessive vasoconstriction.
Platelet count, D-dimer, Doppler surveillance where indicated	thromboembolism signal from ATHOS-3.
Serum creatinine and need for renal replacement	renal outcomes were a notable post hoc finding.
Plasma renin	investigational marker of responders.

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Supplied as 2.5 mg/mL vials (1 mL and 2 mL), diluted in 0.9% sodium chloride to 5,000 or 10,000 ng/mL and infused by pump through a central venous catheter, with continuous invasive arterial pressure monitoring. Hospital-only; the calculator is not applicable.

6Commonly studied alongside

Noradrenaline, vasopressin and adrenaline (the standard vasopressors it is added to), hydrocortisone (adjunct in septic shock), terlipressin (#215) and desmopressin/vasopressin (#107) as related pressor peptides, and apelin and the ACE2/angiotensin-(1-7) axis in experimental counter-regulation.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	FDA-approved December 2017 (Giapreza) to increase blood pressure in adults with septic or other distributive shock
European Union	EMA centrally authorised August 2019 for refractory hypotension in adults with septic or other distributive shock not responding to fluids and catecholamines
United Kingdom	Licensed (grandfathered from the EU authorisation); availability and NHS use limited †
Australia	Not registered on the ARTG †
South Africa	Not registered †
Sport (WADA)	Not prohibited †

8Open questions

Does angiotensin II improve survival, or only blood pressure? A mortality-powered trial has not been completed.
Where it belongs in the sequence of vasopressors relative to vasopressin, and whether renin or ACE activity should guide selection.
Long-term safety of thrombotic and ischaemic complications in survivors.

9References

1Khanna A et al. (2017). Angiotensin II for the treatment of vasodilatory shock (ATHOS-3). NEJM. PubMed · DOI
2Tumlin JA et al. (2018). Outcomes in patients with vasodilatory shock and renal replacement therapy treated with intravenous angiotensin II. Crit Care Med. PubMed · DOI
3Bellomo R et al. (2020). Renin and survival in patients given angiotensin II for catecholamine-resistant vasodilatory shock: a clinical trial. Am J Respir Crit Care Med. PubMed · DOI
4Chawla LS et al. (2014). Intravenous angiotensin II for the treatment of high-output shock (ATHOS trial): a pilot study. Crit Care. PubMed · DOI
5Evans L et al. (2021). Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med / Crit Care Med. PubMed · DOI
6Giapreza (angiotensin II) US prescribing information and EMA Summary of Product Characteristics (current). PubMed

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

10Community

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Self-reported side effects Phase 2

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11Page history

31 Oct 2026Profile published — awaiting medical review

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