Quick summary
Endothelin-1 is a 21-amino acid peptide and the most potent endogenous vasoconstrictor known. FDA-approved receptor antagonists (bosentan, macitentan) for pulmonary arterial hypertension validate it as a key target.
Overview
Endothelin-1 (ET-1) is a 21-amino acid peptide produced primarily by vascular endothelial cells and is the most potent endogenous vasoconstrictor known. It plays critical roles in cardiovascular regulation, pulmonary hypertension pathophysiology, and renal function. Endothelin receptor antagonists (ERAs) such as bosentan and macitentan are FDA-approved treatments for pulmonary arterial hypertension, validating ET-1 as a key therapeutic target.
Mechanism of action
ET-1 is synthesized as a 212-amino acid preproendothelin, cleaved to Big Endothelin-1 (38 AA), then converted to the active 21-AA form by endothelin-converting enzyme (ECE). ET-1 acts on two GPCRs: ETA receptors (predominant on smooth muscle, mediating potent vasoconstriction and proliferation) and ETB receptors (on endothelial cells, mediating transient vasodilation via NO and prostacyclin release; also on smooth muscle mediating contraction). ETA activation is the dominant net effect, producing sustained vasoconstriction via PLC/IP3/DAG signaling and calcium mobilization.
Dosing protocols
| Purpose | Route | Dosage | Frequency | Notes |
|---|---|---|---|---|
| vascular pharmacology research | intravenous | 1–50 pmol/kg/min | continuous infusion per experimental protocol |
Dosing information is for educational purposes only. Consult a qualified healthcare professional before using any peptide.
Research summary
ET-1 is implicated in pulmonary arterial hypertension, systemic hypertension, heart failure, renal disease, and preeclampsia. Multiple FDA-approved ERA drugs (bosentan, ambrisentan, macitentan) demonstrate the therapeutic importance of blocking ET-1 signaling. Research continues on ET-1's role in cancer progression, fibrosis, and neuropathic pain. ET-1 is used as a tool compound to model vascular disease in preclinical studies.[1][2][3]
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 Endothelin-1 for synergistic effects.
Legal status
ET-1 itself is a research compound. Therapeutic interventions targeting ET-1 signaling (endothelin receptor antagonists) are prescription drugs approved for pulmonary arterial hypertension.
Sourcing & access
Research compound
Endothelin-1 is classified as a research compound. Regulatory status varies by jurisdiction. Always verify current legal status and source from vendors providing third-party certificates of analysis (COA).
Frequently asked questions
Endothelin-1 (ET-1) is a 21-amino acid peptide produced primarily by vascular endothelial cells. It is the most potent endogenous vasoconstrictor known and plays critical roles in cardiovascular regulation, pulmonary hypertension pathophysiology, and renal function.
ET-1 acts on two GPCRs: ETA receptors on smooth muscle (mediating potent vasoconstriction and proliferation) and ETB receptors on endothelial cells (mediating transient vasodilation via NO release). ETA activation is the dominant net effect, producing sustained vasoconstriction via PLC/IP3/DAG signaling and calcium mobilization.
ET-1 itself is a research compound with severe effects including hypertension, coronary vasospasm, renal vasoconstriction, and bronchoconstriction. Endothelin receptor antagonists that block ET-1 signaling (bosentan, ambrisentan, macitentan) are FDA-approved prescription drugs with established safety profiles.
Multiple endothelin receptor antagonists are FDA-approved for pulmonary arterial hypertension: bosentan (dual ETA/ETB), ambrisentan (ETA-selective), and macitentan (dual ETA/ETB). These drugs block the vasoconstriction and vascular remodeling caused by excess ET-1 signaling in the pulmonary vasculature.