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#97

Angiotensin II

CardiovascularGiaprezaAngiotensin II InjectionANG IIHypertensin

A synthetic form of the naturally occurring octapeptide hormone that regulates blood pressure through potent vasoconstriction, FDA-approved as a vasopressor for the treatment of refractory distributive shock.

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Overview

Angiotensin II is a synthetic form of the naturally occurring octapeptide (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe) that is the primary effector molecule of the renin-angiotensin-aldosterone system (RAAS). In normal physiology, angiotensin II is produced through sequential enzymatic cleavage: renin converts angiotensinogen to angiotensin I, which is then converted to angiotensin II by angiotensin-converting enzyme (ACE). Angiotensin II acts on AT1 receptors to cause potent vasoconstriction, aldosterone secretion, sympathetic nervous system activation, and ADH release.

Approved by the FDA in December 2017 as Giapreza, synthetic angiotensin II is indicated for the treatment of hypotension in adults with septic or other distributive shock who remain hypotensive despite adequate fluid resuscitation and conventional vasopressor therapy. This made angiotensin II the first new vasopressor mechanism approved in over a decade, addressing an important unmet need in critical care medicine.

The ATHOS-3 (Angiotensin II for the Treatment of High-Output Shock) trial was the pivotal study that led to FDA approval. This randomized, double-blind, placebo-controlled trial enrolled patients with vasodilatory shock requiring high-dose conventional vasopressors. Angiotensin II was significantly superior to placebo in achieving the primary endpoint of a mean arterial pressure (MAP) increase of ≥10 mmHg or achieving MAP ≥75 mmHg at hour 3, with 69.9% of angiotensin II patients achieving target MAP versus 23.4% on placebo.

The rationale for angiotensin II as a vasopressor is particularly compelling in patients with septic shock who may have relative RAAS insufficiency due to reduced ACE activity (ACE is heavily concentrated in the pulmonary endothelium, which is often damaged in sepsis). Additionally, angiotensin II acts through a completely different receptor pathway (AT1 receptors) than catecholamine vasopressors (adrenergic receptors) and vasopressin (V1 receptors), providing a complementary mechanism when conventional vasopressors fail.

Research Uses & Applications

  • FDA-approved treatment of hypotension in distributive (septic) shock refractory to conventional vasopressors
  • Adjunctive vasopressor in catecholamine-resistant shock
  • Investigated for potential renal benefits in patients with acute kidney injury requiring renal replacement therapy
  • Research into RAAS physiology in critical illness
  • Studied as a predictor of angiotensin II responsiveness based on ACE activity and renin levels
  • Historical use in renovascular hypertension diagnostic testing (angiotensin II infusion test)

Key Research Findings

  • The ATHOS-3 trial demonstrated angiotensin II achieved target MAP response in 69.9% vs 23.4% placebo at 3 hours in refractory vasodilatory shock (NEJM, 2017).
  • Post-hoc analysis of ATHOS-3 suggested potential survival benefit in patients with high baseline renin levels, reflecting greater RAAS insufficiency.
  • Subgroup analysis showed angiotensin II-treated patients requiring renal replacement therapy had improved survival and greater likelihood of RRT discontinuation.
  • Research demonstrated that ACE activity is often impaired in sepsis due to pulmonary endothelial injury, providing a physiological rationale for exogenous angiotensin II.
  • Studies showed angiotensin II allows reduction in catecholamine vasopressor doses, potentially reducing catecholamine-associated adverse effects.

Risks & Side Effects

  • Thromboembolic events (arterial and venous) reported; concurrent venous thromboembolism prophylaxis is recommended.
  • Risk of excessive vasoconstriction leading to peripheral and organ ischemia.
  • Tachycardia and arrhythmias reported in clinical trials.
  • Potential for fungal infections observed at higher rates in the angiotensin II group in ATHOS-3.
  • Must be administered with continuous hemodynamic monitoring in an ICU setting.

Administration

Administered as continuous intravenous infusion. Starting dose: 20 ng/kg/min. Titrated every 5 minutes by increments of up to 15 ng/kg/min as needed to achieve target MAP, up to a maximum of 80 ng/kg/min during the first 3 hours. After 3 hours, maintenance dose should not exceed 40 ng/kg/min. Dose should be reduced once underlying shock improves. Administered only in ICU settings with invasive arterial blood pressure monitoring.

Legal Status

FDA-approved prescription medication marketed as Giapreza. Approved for refractory distributive shock. Restricted to hospital/ICU use. Manufactured by La Jolla Pharmaceutical Company (now Innoviva). Not a controlled substance.

Frequently Asked Questions

What is Angiotensin II?

A synthetic form of the naturally occurring octapeptide hormone that regulates blood pressure through potent vasoconstriction, FDA-approved as a vasopressor for the treatment of refractory distributive shock.

What are the main uses of Angiotensin II?

The primary research applications of Angiotensin II include: FDA-approved treatment of hypotension in distributive (septic) shock refractory to conventional vasopressors; Adjunctive vasopressor in catecholamine-resistant shock; Investigated for potential renal benefits in patients with acute kidney injury requiring renal replacement therapy; Research into RAAS physiology in critical illness; Studied as a predictor of angiotensin II responsiveness based on ACE activity and renin levels; Historical use in renovascular hypertension diagnostic testing (angiotensin II infusion test).

What are the risks and side effects of Angiotensin II?

Documented risks and side effects include: Thromboembolic events (arterial and venous) reported; concurrent venous thromboembolism prophylaxis is recommended.; Risk of excessive vasoconstriction leading to peripheral and organ ischemia.; Tachycardia and arrhythmias reported in clinical trials.; Potential for fungal infections observed at higher rates in the angiotensin II group in ATHOS-3.; Must be administered with continuous hemodynamic monitoring in an ICU setting.. Always consult a healthcare professional before considering any peptide.

Is Angiotensin II legal?

FDA-approved prescription medication marketed as Giapreza. Approved for refractory distributive shock. Restricted to hospital/ICU use. Manufactured by La Jolla Pharmaceutical Company (now Innoviva). Not a controlled substance.

How is Angiotensin II administered?

Administered as continuous intravenous infusion. Starting dose: 20 ng/kg/min. Titrated every 5 minutes by increments of up to 15 ng/kg/min as needed to achieve target MAP, up to a maximum of 80 ng/kg/min during the first 3 hours. After 3 hours, maintenance dose should not exceed 40 ng/kg/min. Dose should be reduced once underlying shock improves. Administered only in ICU settings with invasive arterial blood pressure monitoring.

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The information on this page is for educational and informational purposes only. It is not intended as medical advice. Always consult a qualified healthcare professional before considering any peptide or supplement. 50 Best Limited does not endorse, recommend, or promote the use of any peptide for self-administration. Read our full disclaimer.

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