title: PD156707: a potent antagonist of endothelin-1 in human diseased coronary arteries and vein grafts.
abstract: We have determined the ability of the endothelin A (ETA)-selective antagonist PD156707 to block constrictor ET-1 responses in blood vessels from the diseased human heart. ET-1 potently contracted nonatherosclerotic coronary arteries from patients with cardiomyopathy (pD2 = 7.96 +/- 0.15; n = 6), atherosclerotic coronary arteries from patients with ischemic heart disease (pD2 = 8.26 +/- 0.20; n = 4), and saphenous vein grafts that had developed "atherosclerotic" disease after coronary artery bypass (pD2 = 8.41 +/- 0.09; n = 6). PD156707 (100 nM) antagonized the vasoconstrictor response to ET-1 in each of the three preparations, with estimated pA2 values of 7.91 +/- 0.20, 8.05 +/- 0.14, and 8.07 +/- 0.02, respectively. These data suggest that the upregulation of ETB receptors that has been reported in human atherosclerotic coronary arteries does not contribute significantly to the ET-1-mediated constrictor response in these vessels in vitro.
authors.affiliation: Clinical Pharmacology Unit, University of Cambridge, Addenbrooke's Hospital, England.
authors.forename: J J
authors.initials: JJ
authors.lastname: Maguire
authors.forename: A P
authors.initials: AP
authors.lastname: Davenport
mesh_terms: D000328:Adult; D001158:Arteries / Q000187:drug effects / Q000637:transplantation; D001161:Arteriosclerosis / Q000503:physiopathology; D001026:Coronary Artery Bypass; D003327:Coronary Disease / Q000503:physiopathology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000637:transplantation; D004149:Dioxoles / Q000494:pharmacology*; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D044022:Receptor, Endothelin A; D012501:Saphenous Vein / Q000187:drug effects / Q000637:transplantation
chemical_list: D004149:Dioxoles; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; C093321:PD 156707; D044022:Receptor, Endothelin A