Quick summary
Angiotensin II is the primary RAAS effector and a potent vasoconstrictor. Giapreza (synthetic form) is FDA-approved for distributive shock in ICU patients, supported by the ATHOS-3 trial.
Overview
Angiotensin II is an endogenous octapeptide and the primary effector of the renin-angiotensin-aldosterone system (RAAS). It is a potent vasoconstrictor that regulates blood pressure, fluid balance, and cardiovascular homeostasis. The synthetic form (Giapreza) received FDA approval in 2017 for treatment of distributive shock in critically ill patients who fail catecholamine therapy.
Mechanism of action
Angiotensin II binds primarily to AT1 receptors on vascular smooth muscle and the adrenal cortex. AT1 activation triggers Gq-mediated signaling leading to vasoconstriction, aldosterone secretion, sodium and water retention, and sympathetic nervous system potentiation. These combined effects rapidly increase mean arterial pressure. AT2 receptors mediate opposing vasodilatory and anti-proliferative effects. In septic shock, exogenous Ang II restores vasomotor tone and reduces catecholamine requirements.
Dosing protocols
| Purpose | Route | Dosage | Frequency | Notes |
|---|---|---|---|---|
| distributive shock (ICU, Giapreza) | intravenous | 20–200 ng/kg/min | continuous IV infusion, titrated to MAP response | Starting dose 20 ng/kg/min, titrate every 5 minutes. Max dose 200 ng/kg/min in first 3 hours, then max 80 ng/kg/min. |
Dosing information is for educational purposes only. Consult a qualified healthcare professional before using any peptide.
Research summary
The FDA approval of Giapreza was supported by the ATHOS-3 trial (2017), a randomized controlled trial demonstrating that Angiotensin II significantly increased MAP in patients with distributive shock compared to placebo. Research continues on Ang II's roles in cardiac remodeling, renal function, and as a therapeutic target in hypertension, heart failure, and COVID-19 (ACE2 receptor modulation). Extensive evidence base from decades of RAAS pharmacology.[1][2][3][4]
Evidence grading
Each claimed benefit is graded by the strength of available evidence. Grades reflect study quality, not effect size.
Strong = multiple RCTs · Moderate = limited trials or observational · Preliminary = animal or in vitro only · Insufficient = anecdotal or no published data
Side effects
Side effects vary by individual. This is not an exhaustive list. Report unusual symptoms to a healthcare professional.
Common stacks
Peptides commonly paired with Angiotensin II for synergistic effects.
Legal status
Giapreza (angiotensin II injection) is FDA-approved as a prescription vasopressor for adults with distributive shock. Hospital-administered only under ICU monitoring.
Sourcing & access
Prescription required
Angiotensin II is an FDA-approved prescription medication available through licensed healthcare providers, telehealth platforms, and 503A/503B compounding pharmacies.
Frequently asked questions
Angiotensin II is an endogenous octapeptide and the primary effector of the renin-angiotensin-aldosterone system (RAAS). It is a potent vasoconstrictor that regulates blood pressure, fluid balance, and cardiovascular homeostasis. The synthetic form Giapreza received FDA approval in 2017.
Angiotensin II binds AT1 receptors on vascular smooth muscle and adrenal cortex, triggering Gq-mediated vasoconstriction, aldosterone secretion, sodium and water retention, and sympathetic nervous system potentiation. AT2 receptors mediate opposing vasodilatory effects. In septic shock, exogenous Ang II restores vasomotor tone.
Giapreza is FDA-approved but carries risks of thromboembolism, thrombocytopenia, hypertension from excess dosing, peripheral ischemia, and heart rate changes. It is hospital-administered only under ICU monitoring with careful dose titration starting at 20 ng/kg/min.
Giapreza is FDA-approved for adults with distributive shock (primarily septic shock) who remain hypotensive despite adequate fluid resuscitation and catecholamine vasopressors. The ATHOS-3 trial demonstrated significant improvements in mean arterial pressure compared to placebo in this critically ill population.
Research references
- Angiotensin II receptor blockers in hypertension: mechanism and clinical usePubMed
- Angiotensin II vasopressor for refractory vasodilatory shock: ATHOS-3 trialPubMed
- Renin-angiotensin system in cardiovascular regulation: physiology and pathologyPubMed
- Angiotensin II and aldosterone in chronic kidney disease and heart failurePubMed