The human heart endothelin system: ET-1 synthesis, storage, release and effect

Abstract

Endothelin-1 (ET-1) is synthesized, stored and released in the human heart. On release, ET-1 has the potential to activate specific receptors in a paracrine manner to modify heart function directly. Two binding sites corresponding to endothelin ETA and ETB receptors are localized to human heart. Contractility is modified by ETA receptors in the left ventricle and by ETA and ETB receptors, and a receptor that is possibly a different conformation of ETA and/or ETB receptors, in the right atrium. The endothelin system might directly support the failing heart but might also contribute to its pathology, providing a basis for the therapeutic use of endothelin receptor antagonists.