Endothelin-1 and endothelin receptor antagonists in cardiovascular remodeling.
Endothelins build a peptide family composed of three isoforms, each of them containing 21 amino acids. Endothelin-1 is the isoform mainly responsible for any cardiovascular action and therefore the sole scope of this review. Endothelin-1 is the most potent endogenous vasoconstrictor known; in addition it acts as a potent (co)mitogen. There is a substantial body of experimental evidence that endothelin-1 may contribute not only to sustained vasoconstriction, but also to remodeling within the cardiovascular system. Thus, with the help of endothelin receptor antagonists (available for a few years) the involvement of mainly ETA receptors in structural diseases such as heart failure, pulmonary hypertension, atherosclerosis, restenosis, systemic hypertension, and chronic renal failure has been shown. These data make endothelin receptor antagonists, and especially those selective for the ETA receptor, promising agents for the treatment of chronic cardiovascular diseases associated with remodeling. Currently several chemically distinct, orally available members of this novel class of therapeutic agents are under clinical investigation.
Kirchengast
M
M
Department of International Strategic Marketing Cardiovascular, Knoll AG, D-67008 Ludwigshafen, Germany. michael.kirchengast@knoll-ag.de
Münter
K
K
D000818:Animals; D001161:Arteriosclerosis / Q000188:drug therapy; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000209:etiology; D002319:Cardiovascular System / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism*; D006333:Heart Failure / Q000188:drug therapy; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology; D051381:Rats; D014662:Vasoconstrictor Agents / Q000378:metabolism
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D014662:Vasoconstrictor Agents