Discovery to drug development in under a decade

The function of the vascular endothelium has become a major focus of research. This is partly because of the success of drugs (such as the angiotensin converting enzyme inhibitors, the nitrovasodilators, and aspirin) which act through mechanisms related to endothelial function, and partly because endothelial dysfunction is now thought to be an important early factor predisposing to atherogenesis.1

Endothelin-1 is a recently discovered endothelium derived vasoconstrictor and pressor peptide with mitogenic properties,2 which is now recognised to influence basal vascular tone and blood pressure.3 Endothelin antagonists are currently in development and may provide an important new approach to the treatment of cardiovascular disease.4

Endothelin-1 is generated from an inactive precursor, “big” endothelin-1, through the action of a unique endothelin converting enzyme. The mature peptide acts on endothelin type A and endothelin type B receptors. In blood vessels, endothelin-1 causes vasoconstriction largely through stimulating the endothelin type A receptor on smooth muscle cells, although type B receptors …