Endothelin and its isoforms have been extensively studied for 5 years, yet a clear pathophysiological role for this family of potent vasoconstrictor peptides has yet to be identified.
The existence of a powerful endogenous endotheliumderived vasoconstrictor was predicted from the early 1980s, but not until 1988 did Yanagisawa and colleagues first report the identification of a 21 aminoacid peptide, endothelin (ET), from the supernatant of cultured porcine aortic endothelial cells 1. Within a year, two further ET isoforms were described (ET-2 and ET-3), their existence having been predicted from the study of cDNA libraries isolated from several species 2, and today, no more potent vasoconstrictors have been discovered. The sarafotoxins, which are the envenoming agents of the Israeli burrowing asp, have a very high degree of sequence homology with ET, and share its effects 1. These include, in animals, initial transient vasodilatation (via endothelial cell surface receptors and interaction with endotheliumderived relaxing factors), then intense and unusually long-lasting vasoconstriction (via receptors on smooth muscle), positive inotropy and arrhythmogenesis 3. ET is synthesised not only by the endothelial lining of vessels in a wide variety of tissues and across many species, but also by a range of cultured cells 4, including those of epithelial, smooth muscle, mesangial, malignant and neural origin. However despite 5 years of intensive study and the publication of more than 2500 papers, a clear pathophysiological role for this family of peptides has yet to be identified.
Karet et al. (Sat,) conducted a review in Endothelin physiology. Endothelin was evaluated. Endothelin and its isoforms have been extensively studied for 5 years, yet a clear pathophysiological role for this family of potent vasoconstrictor peptides has yet to be identified.