The role of endothelin in the vessel wall

Endothelins (ETs) are a family of vasoactive peptides occurring in three isoforms (ET-1, ET-2, ET-3) encoded by three distinct genes in the human genome. ETs arise from precursor peptides (big-ETs) that are cleaved and released by an endothelin-converting enzyme. ET-1 secretion, which can be stimulated by various agents, is preferentially directed towards the abluminal site of endothelial cells, suggesting a local paracrine action of the peptide. ETs exert their actions through the activation of at least two receptor subtypes: ET-A receptors, which mediate the proliferative and vasoconstrictive effects, and ET-B receptors, which mediate vasorelaxation. Although, the potential roles of ETs are mostly hypothetical, considering their potent cardiovascular effects, it has been suggested that maintenance of a basal vascular tone and regulation of vascular growth and haemostasis may well represent the biological functions of this family of peptides. The recent discovery of specific receptor antagonists will provide a means to assess their physiological and pathophysiological roles.