ABSTRACT
Endothelin-1 is the most potent vasoconstrictor and pressor agent currently identified and was originally isolated and characterized by Yanagisawa and colleagues (1988) from the culture media of aortic endothelial cells. Subsequently, two further isoforms, termed endothelin-2 and endothelin-3, were identified along with structural homologues isolated from the venom of Actractaspis engaddensis, known as the sarafotoxins. Each of the mature isoforms consists of 21 amino acids linked by two constraining intra-chain disulphide bonds. A highly conserved C-terminal sequence is mandatory for biological function of the peptide (Figure 2.1). Although the isoforms are structurally similar, endothelin-1 appears to be the predominant isoform involved in cardiovascular regulation and is the only isoform produced constirutively by endothelial cells (Inoue et al., 1989). The rapid development of selective endothelin receptor antagonists has led to an explosion of research in this field. This work has demonstrated the therapeutic potential for pharmacological manipulation of the endothelin system in a range of cardiovascular conditions.
