THE ENDOTHELIN SYSTEM AND ITS POTENTIAL AS A THERAPEUTIC TARGET IN CARDIOVASCULAR-DISEASE

Endothelin (ET)-1, an endothelium-derived peptide, is the most potent vasoconstrictor agent described to date. ET-I also has positive inotro pic and chronotropic effects in the heart and is a co-mitogen in both cardiac and vascular myocytes. The major elements of the system involv ed in formation of ET-1 and its isopeptides, as well as the receptors mediating their effects, have been cloned and characterised. Antagonis ts of the ET receptors are now available, and selective inhibitors of the ET-converting enzymes are being developed. Early studies using rec eptor antagonists support the involvement of ET-1 in the pathophysiolo gy of several cardiovascular diseases. The relative merits of ET-conve rting enzyme inhibitors and receptor antagonists for the treatment of cardiovascular disease are discussed. Copyright (C) Elsevier Science I nc.