Endothelin-1

Summary

Endothelin-1 (ET-1) is the most potent endogenous vasoconstrictor known, produced primarily by vascular endothelial cells. It plays a central role in cardiovascular homeostasis and is implicated in the pathophysiology of pulmonary arterial hypertension, heart failure, hypertension, renal disease, and cancer. It is not used therapeutically but serves as a key pharmacological target; endothelin receptor antagonists (e.g., bosentan, ambrisentan, macitentan) are approved drugs that block its effects.

Mechanism of Action

Endogenous 21-amino acid peptide that binds ETA and ETB receptors on vascular smooth muscle and endothelial cells, causing potent and sustained vasoconstriction (primarily via ETA), as well as modulation of cell proliferation, inflammation, and fibrosis. ETB receptor activation on endothelial cells promotes vasodilation via nitric oxide and prostacyclin release.

Routes of Administration

Goals & Uses

• Research tool for vasoconstriction studiesResearchHigh
• Model of renal vasoconstriction and injuryResearchModerate
• Pharmacological target for PAH treatmentTherapeutic TargetHigh
• Cancer biology research (tumor angiogenesis)ResearchModerate
• Biomarker for pulmonary arterial hypertensionDiagnostics / BiomarkerHigh

Contraindications

• Systemic administration in humans outside controlled researchGeneralHigh
• Coronary artery diseaseCardiovascularHigh
• Renal impairmentOrgan DysfunctionHigh
• Pre-existing severe hypertensionCardiovascularHigh

Adverse Effects

• Pulmonary vasoconstrictionPulmonaryCommon
• Nausea and flushingGeneralCommon
• Myocardial ischemia / coronary vasospasmCardiovascularUncommon
• BronchoconstrictionRespiratoryUncommon
• Severe vasoconstriction / hypertensionCardiovascularCommon
• Renal vasoconstriction and reduced GFRRenalCommon

Drug Interactions

• Endothelin receptor antagonists (bosentan, ambrisentan, macitentan)High
• Vasopressors (e.g., norepinephrine, vasopressin)High
• Nitric oxide donors / nitratesModerate
• ACE inhibitorsLow

Population Constraints

• Patients with heart failureCardiovascularAbsolute
• Patients with chronic kidney diseaseRenalRelative
• Pregnant womenReproductiveAbsolute
• Neonates and pediatric populationsPediatricAbsolute

Regulatory Status

• European UnionUnapprovedNot approved by EMA as a therapeutic agent. Used only in controlled research settings.
• United StatesUnapprovedNot an approved therapeutic; classified as a research peptide. Endothelin pathway antagonists (not ET-1 itself) are FDA-approved for PAH.
• United KingdomUnapprovedNot approved by MHRA as a medicine. Used as a research tool only.

ET-1 itself is not an approved therapeutic agent. It is used as a research/experimental tool. Endothelin receptor antagonists targeting the ET-1 pathway are FDA/EMA-approved for pulmonary arterial hypertension.

Evidence & Sources

No sources recorded yet.