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-1 also has positive inotropic and chronotropic effects in the heart and is a co-mitogen in both cardiac and vascular myocytes. The major elements of the system involved in formation of ET-1 and its isopeptides, as well as the receptors mediating their effects, have been cloned and characterised. Antagonists of the ET receptors are now available, and selective inhibitors of the ET-converting enzymes are being developed. Early studies using receptor antagonists support the involvement of ET-1 in the pathophysiology of several cardiovascular diseases. The relative merits of ET-converting enzyme inhibitors and receptor antagonists for the treatment of cardiovascular disease are discussed.
Gray
G A
GA
Department of Pharmacology, University of Edinburgh, Scotland.
Webb
D J
DJ
D000595:Amino Acid Sequence; D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D002320:Cardiovascular Physiological Phenomena; D019332:Endothelin-1 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D017466:Receptors, Endothelin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
D019332:Endothelin-1; D017466:Receptors, Endothelin