Angiotensin II

In plain language

Angiotensin II is the body's main blood-pressure-raising hormone, an eight-amino-acid chain produced by the renin-angiotensin system. Decades of blood-pressure drugs (ACE inhibitors, ARBs) exist to block it, which makes it surprising that it was approved in 2017 as a drug itself.

As Giapreza, it is given intravenously in intensive care to raise blood pressure in patients with distributive shock (such as septic shock) whose pressure remains dangerously low despite fluids and standard medications. The most-studied class of blood-pressure medicines blocks this hormone; this drug is the same molecule, used to do the opposite job.

For students

Angiotensin II is the octapeptide Asp-Arg-Val-Tyr-Ile-His-Pro-Phe (DRVYIHPF, about 1,046 Da), produced by renin cleavage of angiotensinogen to angiotensin I, then ACE conversion to angiotensin II. It acts at AT1 receptors to cause vasoconstriction, aldosterone release, and sympathetic potentiation.

As a drug (Giapreza, La Jolla Pharmaceutical), it is infused intravenously for distributive shock with adequate cardiac output but refractory hypotension. The ATHOS-3 trial randomized 344 patients to angiotensin II or placebo alongside conventional vasopressors; significantly more angiotensin II patients achieved the blood pressure target (63% versus 23%). Concerns include thrombosis (prophylaxis recommended), and subgroup analyses suggested benefit in patients with higher baseline angiotensin II and renin values.

For researchers and instructors

Biochemistry. The AT1 receptor is a G-protein-coupled receptor; the drug leverages identical receptor pharmacology that ARBs block, illustrating that the same target can be agonized or antagonized for opposite clinical ends.

Pharmacology. Onset within minutes, half-life under a minute (continuous infusion 20 ng/kg/min starting dose, titrated); can cause venous thromboembolism, deep vein thrombosis and arterial thrombosis; used with prophylactic anticoagulation.

Human evidence. ATHOS-3 is the pivotal randomized trial (blood pressure co-primary endpoint met); registry and retrospective data support mortality benefit in high-renin subgroups, but this remains exploratory.

Teaching point. The clearest example of a natural hormone used as a drug in the direction opposite to the main drug class built against it; also teaches the interpretive gap between blood pressure targets and mortality.