Endothelin-1

Where it comes from

Made in

Endothelial cells, mostly toward the underlying muscle rather than into blood; also kidney, lung, neurons

Sent out by

Made on demand from big endothelin-1 by endothelin-converting enzyme; shear stress, hypoxia, angiotensin II and thrombin raise it

Acts on

• Vascular smooth muscle
• Heart muscle
• Kidney
• Lung vessels

What it does

• Constricts arteries for hours, far longer than noradrenaline
• Drives the growth and scarring of vessel walls and heart
• Retains sodium and raises blood pressure when overactive

In medicine

• Endothelin receptor blockers bosentan (2001) ¹, ambrisentan and macitentan treat pulmonary arterial hypertension
• Aprocitentan (2024) treats blood pressure that other medicines do not control ²; sparsentan (2023) and atrasentan (2025) treat IgA nephropathy
• Bosentan is approved in Europe to reduce new finger ulcers in systemic sclerosis

Beyond the body’s own use

• Blocking endothelin does not help heart failure: in 1,613 patients with severe chronic heart failure bosentan brought early fluid retention and more admissions, and changed neither clinical status nor survival ³
• In a randomised trial meant to protect the kidney from contrast dye, an endothelin receptor blocker made the injury worse; that reversal is still cited when the class is proposed for acute kidney injury ⁴
• Fluid retention and raised liver enzymes are the class problems, which is why bosentan needs monthly liver tests and why these medicines are dispensed under restricted programmes ¹³
• Blood endothelin-1 rises in pre-eclampsia, sepsis and heart failure, and is studied as a marker; no assay for it has entered clinical use