title: Endothelin-1 and endothelin receptor antagonists as potential cardiovascular therapeutic agents.
abstract: Endothelin (ET)-1 is an endothelium-derived peptide with potent vasoconstrictor and proliferative properties. The ET system is activated in several cardiovascular disease states associated with functional and structural vascular changes, including hypertension and heart failure. The two ET receptor subtypes are known as ET(A)R and ET(B)R. The former is located mainly on vascular smooth muscle cells and is responsible for mediating vasoconstriction and proliferation. The latter is present predominantly on endothelial cells and mediates vasorelaxation as well as ET-1 clearance. Activation of smooth muscle ET(B)R causes vasoconstriction. Selective ET(A)R antagonists as well as nonselective ET(A)R-ET(B)R antagonists have been developed. Studies with animal models and early-phase clinical trials provided strong evidence that these agents are effective in the treatment of heart failure, essential hypertension, pulmonary hypertension, and atherosclerosis. However, the complexity of biologic effects mediated by two different receptor subtypes complicates therapy with selective versus nonselective ET receptor antagonists. In addition to subtype selectivity and potency, changes in receptor subtype distribution under different pathologic conditions and different patient populations will play a crucial role in the evaluation of these potentially therapeutic drugs.
authors.affiliation: Department of Clinical and Administrative Sciences, University of Georgia College of Pharmacy, Athens, USA. aergul@mail.mcg.edu
authors.forename: Adviye
authors.initials: A
authors.lastname: Ergul
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000503:physiopathology; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000096:biosynthesis*; D006801:Humans; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
chemical_list: D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B