Angiotensin II
Also known as: Ang II, Angiotensin II, angiotensin-2, ATII, Giapreza, human angiotensin II, LY163502
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Summary
Angiotensin II (Giapreza) is a synthetic human angiotensin II approved for vasodilatory shock. It acts on AT1 receptors to produce potent vasoconstriction, raising mean arterial pressure in catecholamine-refractory septic or other distributive shock states.
Mechanism of Action
Ang II binds the type‑1 angiotensin receptor (AT₁) on vascular smooth‑muscle cells, activating G‑protein signalling that increases intracellular calcium and causes rapid vasoconstriction. It also stimulates aldosterone release from the adrenal cortex and promotes sodium‑water retention, contributing to longer‑term blood‑pressure support.
What the Research Shows
A 2024 meta‑analysis of randomized trials of non‑adrenergic vasopressors (vasopressin, terlipressin, selepressin, angiotensin II, methylene blue, hydroxocobalamin) in septic shock found that the class reduced mortality compared with adrenergic therapy alone (risk ratio 0.92). No individual agent, including angiotensin II, reached statistical significance when analysed separately. Angiotensin II was not evaluated in large antihypertensive efficacy reviews, and no kidney‑outcome trials were identified for the peptide itself. Thus, evidence for angiotensin II is limited to its role as part of a heterogeneous group of vasopressors in acute critical‑care settings.
Reported Benefits
When given intravenously, angiotensin II can rapidly increase mean arterial pressure in refractory vasodilatory shock, helping to restore organ perfusion. The pooled data for non‑adrenergic vasopressors suggest a modest mortality advantage in septic shock, indicating that angiotensin II may contribute to that benefit when used as part of combination therapy.
Limitations of the Evidence
The available literature does not isolate angiotensin II’s effect; individual‑agent mortality benefit was not demonstrated. Data are confined to short‑term intensive‑care use, with no evidence for chronic hypertension or outpatient indications. Heterogeneity among trials and lack of head‑to‑head comparisons limit definitive conclusions about efficacy or optimal dosing.
Safety Considerations
Angiotensin II’s potent vasoconstriction can precipitate tissue ischemia, especially in coronary, cerebral or mesenteric beds. Reported adverse‑event profiles in the meta‑analysis were not drug‑specific, so clinicians must monitor for hypertension‑related complications, reduced cardiac output, and potential renal hypoperfusion. Use is restricted to controlled settings with hemodynamic monitoring.
How It Is Administered
The peptide is supplied for intravenous infusion, typically as a lyophilized powder that is reconstituted and administered via a central or peripheral line. Dosing is titrated to achieve target blood‑pressure goals under intensive‑care supervision; no oral or subcutaneous formulations are approved.
Routes of Administration
Goals & Uses
- Hepatorenal Syndrome (investigational)Renal/HepaticLow
- Mean Arterial Pressure IncreaseHemodynamic SupportHigh
- Septic Shock Rescue TherapyCritical CareHigh
- Increase mean arterial pressureHemodynamic SupportHigh
- Catecholamine-Sparing EffectSupportive CareModerate
- Vasodilatory/Distributive Shock ManagementHemodynamic SupportHigh
Contraindications
- Hypersensitivity to angiotensin II or excipientsAllergyHigh
- Concurrent use of ACE inhibitors in certain contextsDrug InteractionModerate
- Hypersensitivity to the drug productImmunologicHigh
- Active myocardial ischemiaCardiovascularHigh
Adverse Effects
- HypertensionCardiovascularCommonHigh blood pressure
- Peripheral ischemiaVascularUncommon
- Thromboembolic eventsCardiovascularUncommon
- Digital ischemiaPeripheral VascularRare
- Fungal infectionInfectiousUncommon
- TachycardiaCardiovascularCommonAbnormally fast heart rate
- Thromboembolic events (DVT, arterial thrombosis)CardiovascularCommon
- Delirium / agitationNeuropsychiatricUncommon
- Hypertension / excessive blood pressure elevationCardiovascularCommon
Drug Interactions
- Norepinephrine / CatecholaminesModerate
- Angiotensin Receptor Blockers (ARBs)Moderate
- ARBs (angiotensin receptor blockers)High
- VasopressinModerate
- ACE inhibitorsModerate
- ACE Inhibitors (e.g., enalapril, lisinopril)Moderate
Population Constraints
- PregnancyReproductive SafetyRelative
- Pediatric patientsAgeRelative
- Patients with pre-existing thromboembolic disordersHematologicRelative
- Pregnant womenReproductiveRelative
- Severe coronary artery diseaseCardiovascularRelative
Regulatory Status
- European UnionUnapprovedNo marketing authorization as of 2024.
- United StatesApprovedApproved: Vasodilatory shock refractory to catecholaminesApproved under FDA label as Giapreza.
- United KingdomApprovedApproved: Vasodilatory shock in adultsApproved by MHRA following EMA approval; post-Brexit maintained authorization.
FDA‑approved (2017) for vasodilatory shock; marketed as Giapreza. Not approved in the EU as of 2024.
Evidence & Sources
- Journal ArticleHighWang N, et al.2025-01-01T00:00:00.000000Z
- Journal ArticleHighKotani Y, et al.2024-01-01T00:00:00.000000Z
- Journal ArticleHighWang N, et al.2026-01-01T00:00:00.000000Z
- Journal ArticleHighXie X, et al.2016-01-01T00:00:00.000000Z
- Journal ArticleHighCarcel C, et al.2023-01-01T00:00:00.000000Z
- Journal ArticleHighBauer SR, et al.2025-01-01T00:00:00.000000Z
Frequently Asked Questions
What clinical situation is angiotensin II approved for?
It is approved for intravenous use in adults with vasodilatory or septic shock who remain hypotensive despite adequate fluid resuscitation and conventional catecholamine therapy.
How does angiotensin II differ from norepinephrine or dopamine?
Angiotensin II works through the AT₁ receptor to cause direct vasoconstriction, whereas norepinephrine and dopamine act on adrenergic receptors. This non‑adrenergic mechanism may allow it to raise pressure without the same tachyarrhythmic risk.
Is angiotensin II useful for chronic high blood pressure?
Current trial data focus on acute shock; there is no evidence from the cited literature that angiotensin II is effective or safe for long‑term hypertension management.
What are the main safety concerns?
Excessive vasoconstriction can lead to organ ischemia, especially in patients with underlying coronary artery disease or peripheral vascular disease. Continuous hemodynamic monitoring is required.
Can angiotensin II be combined with other vasopressors?
Yes, it is often used as part of a multimodal vasopressor strategy. The 2024 meta‑analysis suggests that combining non‑adrenergic agents with catecholamines may improve outcomes, but specific combination benefits for angiotensin II alone were not isolated.
What is Angiotensin II?
Angiotensin II (Giapreza) is a synthetic human angiotensin II approved for vasodilatory shock. It acts on AT1 receptors to produce potent vasoconstriction, raising mean arterial pressure in catecholamine-refractory septic or other distributive shock states.
What is Angiotensin II used for?
Angiotensin II is educationally associated with: Hepatorenal Syndrome (investigational), Mean Arterial Pressure Increase, Septic Shock Rescue Therapy, Increase mean arterial pressure, Catecholamine-Sparing Effect, Vasodilatory/Distributive Shock Management. Educational only — not medical advice.
How is Angiotensin II administered?
Recorded routes of administration: Intravenous.
What are the potential side effects of Angiotensin II?
Reported adverse effects include: Hypertension, Peripheral ischemia, Thromboembolic events, Digital ischemia, Fungal infection, Tachycardia, Thromboembolic events (DVT, arterial thrombosis), Delirium / agitation, Hypertension / excessive blood pressure elevation. This list is not exhaustive — consult a qualified clinician.
Who should avoid Angiotensin II?
Recorded contraindications: Hypersensitivity to angiotensin II or excipients, Concurrent use of ACE inhibitors in certain contexts, Hypersensitivity to the drug product, Active myocardial ischemia. Consult a qualified clinician before use.