Endothelin is a 21-amino acid vasoconstricting peptide that plays a key part in vascular homeostasis. It is one of the strongest vasoconstrictors currently studied. There are three isoforms with varying regions of expression and two key receptor types, ETA and ETB. ETA is found in smooth muscle and binding of Endothelin to ETA increases vasoconstriction and sodium retention. ETB is primarilary located on endothelial cells and activation of this receptor increases natriuresis and diuresis and NO release. Endothelin was isolated from the Israeli Borrowing Asp in a toxin called sarafotoxin.
In a healthy individual a delicate balance between vasoconstriction and vasodilation is maintained by endothelin, calcitonin and other vasoconstrictors on the one hand and nitric oxide, prostacyclin and other vasodilators on the other.
Overproduction of endothelin can cause pulmonary artery hypertension. This can sometimes be treated by the use of an endothelin receptor antagonist such as bosentan or sitaxsentan. The later selectively blocks endothelin A, decreasing the vasoconstrictive actions and allowing for increased beneficial effects of endothelin B stimulation, such as nitric oxide production (although the effects of endothelin B receptors being activated depend on the type of host cells).