Endothelin-1 (ET-1) is a 21-amino-acid peptide (MW ~2491.9 g/mol) produced primarily by vascular endothelial cells. It is the most potent endogenous vasoconstrictor known, with effects lasting hours. While ET-1 itself is not used therapeutically, endothelin receptor antagonists (ERAs) such as bosentan, ambrisentan, and macitentan are FDA-approved for pulmonary arterial hypertension (PAH).
Category: Cardiovascular / Vasoactive. Evidence rating: B (meaningful human data).
Clinical status: Reference peptide. Not used therapeutically. Endothelin receptor antagonists (bosentan, ambrisentan, macitentan) are FDA-approved for pulmonary arterial hypertension.
ET-1 signals through two G-protein-coupled receptors: ETA and ETB. ETA receptors on vascular smooth muscle mediate sustained vasoconstriction via Gq-phospholipase C activation, increasing intracellular calcium and activating Rho kinase. ETB receptors have dual roles: on endothelial cells, they…
Safety considerations: ET-1 is not used as an exogenous therapeutic agent; Endogenous ET-1 overproduction is implicated in pulmonary hypertension, heart failure, chronic kidney disease, and systemic hypertension; Experimental IV ET-1 infusion causes marked vasoconstriction, hypertension, and reduced cardiac output.
Reviewed by the PeptideAtlas Editorial Team.
| Molecular weight | ~2491.9 g/mol |
|---|---|
| CAS number | 60907-30-4 |
| Half-life | ~4-7 minutes (plasma); tissue effects persist hours |
| Production method | synthetic |
| Anti-doping status | not-listed |
| US regulatory status | ET-1 is not an approved drug. Available as research reagent. ERAs approved: bosentan (Tracleer, 2001), ambrisentan (Letairis, 2007), macitentan (Opsumit, 2013) for PAH. |
Related peptides: Angiotensin II, Angiotensin 1-7, Bradykinin.
ET-1 is the most potent endogenous vasoconstrictor and plays a central role in pulmonary arterial hypertension, heart failure, and chronic kidney disease. Three classes of endothelin receptor antagonists (bosentan, ambrisentan, macitentan) are FDA-approved for PAH. ET-1 also serves as a biomarker for cardiovascular disease severity.
ERAs are drugs that block the effects of ET-1. Bosentan is a dual ETA/ETB antagonist. Ambrisentan is selective for ETA. Macitentan is a dual antagonist with improved tissue penetration. All are used for pulmonary arterial hypertension and carry teratogenic risk (pregnancy category X).
ET-1 was isolated from porcine aortic endothelial cell culture supernatant by Yanagisawa et al. and reported in Nature in 1988 (PMID: 2451132). It was identified as a 21-residue peptide with two disulfide bonds and unprecedented vasoconstrictor potency.