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Research Only Cardiovascular & Renal

Endothelin-1

also known as: ET-1, Endothelin

The most powerful vasoconstrictor in the body — an endothelial peptide central to pulmonary hypertension, targeted by bosentan, ambrisentan, and macitentan.

A 21-amino-acid bicyclic peptide constitutively released by vascular endothelium, acting on ETA and ETB receptors to produce sustained vasoconstriction, and the therapeutic target of endothelin receptor antagonists used in pulmonary arterial hypertension.

Mechanism of action

Binds ETA receptors (on vascular smooth muscle → vasoconstriction, proliferation) and ETB receptors (on endothelium → NO/prostacyclin release → transient vasodilation; on smooth muscle → vasoconstriction). Net effect is powerful, sustained vasoconstriction. Also promotes fibrosis, inflammation, and cardiac hypertrophy.

Primary uses

  • Pulmonary hypertension pathophysiology (target of ERA drugs)
  • Vascular biology research
  • Cardiac and renal fibrosis research
  • Biomarker in cardiovascular disease

Typical dosing

Not established

Endogenous hormone. Not administered therapeutically. Endothelin receptor antagonists are the therapeutic class.

Regulatory status

Endothelin-1 itself is not administered therapeutically. Endothelin receptor antagonists (bosentan, ambrisentan, macitentan) are FDA-approved for pulmonary arterial hypertension.

References

  1. [pubmed] Yanagisawa M, et al. "A novel potent vasoconstrictor peptide produced by vascular endothelial cells." Nature, 1988;332:411-415.
  2. [review] Davenport AP, et al. "Endothelin." Pharmacol Rev, 2016;68:357-418.

Related peptides

Angiotensin II

Giapreza — the first new vasopressor class approved in decades. FDA-approved December 2017 (La Jolla Pharmaceutical) for catecholamine-resistant septic / distributive shock based on the ATHOS-3 trial (NEJM 2017, n=321). Engages a third vasoconstrictor pathway (RAAS / AT1) independent of catecholamines and vasopressin — useful when both of those axes are desensitised.

Vasopressin

Vasostrict — the endogenous antidiuretic hormone as an ICU vasopressor. FDA-approved April 2014 for adults with vasodilatory shock (post-cardiotomy, sepsis) who remain hypotensive despite fluids and catecholamines. Works through V1a receptors on vascular smooth muscle — a receptor axis pharmacologically distinct from catecholamine receptors, preserving its vasopressor effect when adrenergic receptors are desensitised.

BNP

The heart failure biomarker — an endogenous cardiac peptide whose blood levels are the gold standard for diagnosing and monitoring heart failure severity.
Disclaimer

This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.