Angiotensin II
Also known as: Giapreza, LJPC-501, Ang II, AT II, angiotensin 2, Ang-2, human angiotensin II, synthetic human angiotensin II
Endogenous vasoconstrictor peptide; renin-angiotensin-aldosterone system (RAAS) agonist; non-catecholamine vasopressor
What it is
Angiotensin II (brand name Giapreza) is used in hospital intensive care units to rescue critically ill adults whose blood pressure has collapsed and stopped responding to standard vasopressor drugs. It is FDA-approved for septic and distributive shock, enabling doctors to stabilize blood pressure while reducing doses of heart-stressing catecholamines like norepinephrine.
The scientific side
angiotensin II is an endogenous octapeptide (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe) that is the principal effector molecule of the renin-angiotensin-aldosterone system (RAAS). It is generated from angiotensin I by angiotensin-converting enzyme (ACE) and exerts its vasopressor and systemic effects primarily through agonism at angiotensin type 1 receptors (AT1R) expressed on vascular smooth muscle, the adrenal cortex, heart, kidneys, and brain. At the vascular level, AT1R activation triggers Gq/11-coupled signaling cascades including phospholipase C activation, inositol trisphosphate-mediated calcium release from the sarcoplasmic reticulum, and protein kinase C activation, producing potent arterial and venous smooth muscle contraction and a dose-dependent rise in systemic vascular resistance without direct chronotropic or inotropic effects on the myocardium — a mechanistically distinct profile from catecholamine vasopressors (PMIDs: 29582666, 32462921). In septic and vasodilatory shock, the endogenous RAAS is markedly dysregulated: circulating renin rises dramatically while endogenous angiotensin II levels are low relative to the degree of hemodynamic compromise due to increased ACE2-mediated degradation and impaired enzymatic conversion. Exogenous synthetic angiotensin II corrects this deficit by directly engaging AT1R, restoring vascular tone independent of adrenergic pathways. In the pivotal ATHOS-3 Phase III RCT (n=321; PMID 28528561), angiotensin II achieved the primary blood pressure endpoint in 69.9% of patients versus 23.4% with placebo (OR 7.95, P<0.001), and significantly reduced cardiovascular SOFA scores at 48 hours. A post-hoc subgroup analysis demonstrated that patients with elevated baseline plasma renin exhibited particularly robust hemodynamic responses, establishing renin as a potential predictive biomarker. Beyond vasopressor effects, AT1R agonism stimulates aldosterone release from the adrenal zona glomerulosa, promoting sodium and water retention to augment intravascular volume. In patients with acute kidney injury (AKI), angiotensin II promotes efferent arteriolar vasoconstriction in glomeruli, which may maintain glomerular filtration pressure and explain the observed reduction in renal replacement therapy initiation (19.0% vs. 32.4%, P=0.015) in the ATHOS-3 trial. Additionally, post-hoc analysis of ATHOS-3 ARDS patients showed significantly improved PaO2/FiO2 ratios with angiotensin II versus placebo, suggesting beneficial modulation of pulmonary vascular tone via AT1R in the lung vasculature.
Class: Endogenous vasoconstrictor peptide; renin-angiotensin-aldosterone system (RAAS) agonist; non-catecholamine vasopressor
Administration & storage
- Administration
- Continuous intravenous infusion via central venous catheter (preferred) or peripheral IV in emergenciesAdministration via syringe pump or volumetric infusion pump with titration capabilityNot for intramuscularsubcutaneousor bolus intravenous injectionShould be administered in an ICU setting with continuous hemodynamic monitoring
- Storage
- Unopened vials: store in refrigerator at 2–8°C (36–46°F). Do not freeze. Protect from light. Once diluted, stable at room temperature for up to 24 hours. Discard any unused portion. Contains no preservative — use immediately after preparation when possible.
- Cautions
- Thromboembolic and ischemic events: Angiotensin II can induce AT1R-mediated platelet activation and vasoconstriction. Deep vein thrombosis (DVT) occurred in 12.9% of angiotensin II patients vs. 5.1% in placebo in ATHOS-3. Venous thromboembolism prophylaxis is recommended for all patients receiving angiotensin II.,Hypertension overshoot: Excessive titration can cause marked blood pressure elevation with risk of organ ischemia. Continuous arterial blood pressure monitoring is mandatory. Dose reduction or discontinuation required if MAP exceeds target.,Interaction with ACE inhibitors and ARBs: Prior ACEi use increases angiotensin II responsiveness (greater pressor effect per dose); prior ARB use decreases responsiveness via AT1R occupancy. Dose adjustments and careful titration required in patients on these medications.,Peripheral ischemia: As with all potent vasoconstrictors, excessive or prolonged angiotensin II use may cause distal extremity ischemia, particularly in patients with pre-existing peripheral vascular disease.,No use outside monitored ICU setting: Giapreza is exclusively an ICU medication. Administration without continuous hemodynamic monitoring and titration capability is unsafe.
Legal & regulatory status
FDA-approved (NDA 209360) as Giapreza (angiotensin II injection) for increasing blood pressure in adults with septic or other distributive shock. Approved December 21, 2017. Administered as continuous intravenous…
Angiotensin II is not listed on the WADA Prohibited List as of the 2024 prohibited substances list. It is a prescription ICU medication administered by healthcare professionals only; it has no known application or use…
Angiotensin II (Giapreza) received conditional authorization by Health Canada for treatment of adults with vasodilatory shock in the intensive care unit setting. Authorization is consistent with the EU approval granted…
What it's studied for
- Vasodilatory (distributive) shock refractory to conventional vasopressors — restoration of mean arterial pressure Phase III RCT
- Catecholamine-sparing vasopressor strategy in critical illness Human observational
- Post-cardiopulmonary bypass vasoplegia after cardiac surgery Mixed
- Catecholamine-resistant vasodilatory shock with concurrent acute kidney injury (AKI) Phase III RCT
- Shock-associated acute respiratory distress syndrome (ARDS) — oxygenation improvement Phase III RCT
- Vasodilatory shock in septic shock — role of RAAS biomarkers in treatment response prediction Human observational
- Septic shock in immunocompromised and neutropenic patients Human observational
Safety signals
- Venous thromboembolic events (DVT / VTE)
- Hypertension overshoot / excessive blood pressure elevation
- Peripheral tissue ischemia and distal limb ischemia
- Tachycardia and cardiac arrhythmias at high doses
- Interactions with RAAS-modifying medications (ACE inhibitors, ARBs)
- Altered renal hemodynamics — potential for renal cortical ischemia with high-dose use
- Risk of worsening outcomes in patients with severe hypovolemia if not adequately volume resuscitated
Frequently asked
What is angiotensin II (Giapreza) approved for?
Angiotensin II (brand name Giapreza) is FDA-approved to increase blood pressure in adults with septic or other distributive shock. It is a hospital-only medication given by continuous intravenous infusion in intensive care units when standard vasopressors such as norepinephrine have not adequately restored blood pressure. It is not approved or available for outpatient or non-ICU use.
How is angiotensin II different from norepinephrine and other vasopressors?
Angiotensin II is a non-catecholamine vasopressor that works through a completely different receptor pathway than norepinephrine, epinephrine, or vasopressin. It activates angiotensin type 1 receptors (AT1R) on vascular smooth muscle to produce vasoconstriction without directly stimulating the heart (no chronotropic or inotropic effect). This makes it useful as an add-on agent that can raise blood pressure while allowing doctors to reduce doses of catecholamines, potentially lowering the risks of catecholamine-related side effects such as arrhythmias and myocardial stress. Clinical trials showed it reduces catecholamine requirements alongside effective blood pressure restoration.
Does angiotensin II improve survival in septic shock?
The main ATHOS-3 Phase III trial found a trend toward lower 28-day mortality with angiotensin II (46%) versus placebo (54%), but this did not reach statistical significance (HR 0.78; P=0.12). The trial was not powered for a mortality endpoint. Post-hoc analyses suggest that specific subgroups — particularly patients with elevated renin at baseline, those initiating treatment at lower vasopressor doses, and those with stage 3 acute kidney injury — may have a survival benefit (PMIDs: 37147690, 39671552). Definitive survival benefit across all shock patients has not been established in a prospectively powered trial.
What are the main risks of angiotensin II infusion?
The most clinically notable risk identified in clinical trials is venous thromboembolism (DVT occurred in 12.9% of angiotensin II patients vs. 5.1% with placebo in ATHOS-3; PMID 28528561), which is why VTE prophylaxis is recommended. Other risks include excessive blood pressure elevation if not carefully titrated, peripheral ischemia at high doses, and modified dose requirements in patients on ACE inhibitors or angiotensin receptor blockers. Continuous hemodynamic monitoring in an ICU is mandatory.
Can angiotensin II be used in patients with kidney injury?
Yes, and there is emerging evidence it may benefit patients with severe (stage 3) acute kidney injury. A post-hoc analysis of ATHOS-3 found that angiotensin II was associated with significantly lower 28-day mortality and fewer days requiring renal replacement therapy in patients with stage 3 AKI. The full ATHOS-3 trial also showed lower rates of new renal replacement therapy initiation with angiotensin II versus placebo (19.0% vs. 32.4%, P=0.015; PMID 40548153). These findings are hypothesis-generating and prospective trials in AKI-focused populations are needed.
Is angiotensin II used outside the hospital or for bodybuilding/performance purposes?
No. Angiotensin II (Giapreza) is an exclusively hospital-administered ICU medication for critically ill patients with life-threatening shock. It requires continuous monitoring, specialized equipment, and medical expertise to administer safely. It has no established, studied, or approved use outside the ICU setting, and no role in sports performance, bodybuilding, or any non-critical-illness context. Its use outside hospital settings would be medically dangerous.