Endothelin (ET) is a potent vasoconstrictor peptide that is generated via unique processing of a low activity precursor, big ET-1 by endothelin converting enzymes (ECEs). ET has a physiological role in the maintenance of basal tone in humans (Haynes & Webb, 1994; Haynes, 1995; Haynes et al., 1995), but may also have a role in the pathophysiology of cardiovascular diseases, including atherosclerosis, coronary vasospasm and congestive heart disease (Kurihara et al., 1989; Bacon et al., 1996; Cohn, 1996). The ET system is therefore a potential therapeutic target in the effective management of these diseases. There are two current strategies being pursued to attenuate adverse haemodynamic effects and the migration and proliferation of vascular smooth muscle cells by ET. These include the use of antagonists to receptors that mediate responses to ET and the use of selective inhibitors to ECE. The pathways involved in big ET-1 processing and ET transport are only now being elucidated and these findings will be useful in predicting the characteristics of inhibitors that best suit inhibition of ECE. It will be important to determine whether ECE is expressed on the cell surface and/or intracellularly to decide whether inhibitors are required to penetrate the plasma membrane. This article reviews the secretory pathways involved in ET transport and the subcellular processing of big ET-1 by ECE.

ECEs are membrane-bound proteases with structural homology to neutral endopeptidase 24.11 (NEP) and Kell blood group protein (for review, see Opgenorth et al., 1992; Turner, 1993; Turner & Murphy, 1996). The cDNA sequences of two converting enzymes, ECE-1 and ECE-2 have been reported (Schmidt et al., 1994; Emoto & Yanagisawa, 1995;