At a glance

What is angiotensin II?

Angiotensin II is a peptide hormone made of eight amino acids that the body uses to control blood pressure, and a synthetic form of it is used as a drug. It is the main active molecule of the renin-angiotensin system¹, the hormone cascade that regulates blood pressure and fluid balance.

As a medicine, it is a laboratory-made copy of the human hormone, developed by La Jolla Pharmaceutical, now part of Innoviva, and sold as Giapreza². It is given only as a continuous intravenous infusion in a hospital, not as an injection a person takes at home.

The history of angiotensin II

Angiotensin II was discovered twice at once, and that is how it got its name. The table below traces it from discovery to approval.

For most of the following decades, the molecule was studied as a hormone and as a target to block, since many common blood-pressure medicines (ACE inhibitors¹ and ARBs) work by reducing its activity. Using the hormone itself as a treatment came much later, when it was developed as an intravenous drug for shock.

How does angiotensin II work?

Angiotensin II raises blood pressure by binding to receptors on the muscle lining the blood vessels and making them tighten. It acts mainly through the AT1 receptor⁴ on vascular smooth muscle, and activating it constricts the vessels, which raises blood pressure quickly. This is the final active step of the renin-angiotensin system: the kidney releases renin, which starts a chain that produces angiotensin I, and an enzyme called ACE converts that into angiotensin II, the potent form.

Beyond directly tightening vessels, angiotensin II signals the adrenal glands to release aldosterone, a hormone that makes the body hold on to sodium and water, and it promotes the release of vasopressin, another blood-pressure hormone. In shock, this matters because it gives clinicians a way to raise blood pressure through a pathway separate from the standard catecholamine drugs such as norepinephrine, which helps when those drugs alone are not enough.

In the pivotal ATHOS-3 trial⁵ of patients with vasodilatory shock who were already on high-dose vasopressors, adding angiotensin II raised blood pressure to the target in 69.9% of patients, compared with 23.4% on placebo. It is given as a continuous infusion and adjusted to blood pressure, and because the peptide is cleared from the blood within about a minute, its effect can be dialed up or down quickly.

Is it FDA-approved?

Yes. The FDA approved⁴ angiotensin II as Giapreza in December 2017 to increase blood pressure in adults with septic or other distributive shock. It was a notable approval because it introduced a new type of vasopressor, giving intensive care teams a hormone-based option to add when standard drugs are not controlling dangerously low blood pressure.

What is angiotensin II prescribed for?

Angiotensin II is prescribed in the intensive care unit to raise blood pressure in adults whose blood pressure is dangerously low from septic or other distributive shock, a state in which the blood vessels lose their tone and dilate. It is typically added on top of standard vasopressors such as norepinephrine and vasopressin for patients who are not responding adequately to those alone, rather than used first. It is a short-term, closely monitored hospital treatment, not an outpatient medication.

What are the side effects?

The most important safety concern is a risk of blood clots. In its trial, angiotensin II was associated with thrombotic events⁴, including deep vein thrombosis, and the label recommends giving clot-prevention treatment (venous thromboembolism prophylaxis) while a patient is receiving it. According to the prescribing information, other reported effects included:

• Low platelet counts
• A fast heart rate
• Fungal infection
• Delirium
• Acidosis
• High blood sugar
• Reduced blood flow to the hands and feet

Because it is used only in intensive care, patients receiving it are already under close monitoring.

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