title: No alteration in vasoconstrictor endothelin-B-receptor density or function in human coronary artery disease.
abstract: We have determined whether vasoconstrictor endothelin-B- (ET(B)) receptors are altered in human coronary artery disease. Variable responses to the ET(B) agonist sarafotoxin S6c (S6c) were obtained in control [cardiomyopathy (CDM), n = 15] and diseased [ischaemic heart disease (IHD), n = 16] coronary arteries, with 40% and 50% of arteries not responding, respectively. S6c potently contracted the remaining vessels with EC50 values of 0.4 nM (95% CI, 0.05-2.8 nM) in CDM (n = 9/15) and 1.1 nM (95% CI 0.2-9.2 nM) in IHD (n = 8/16) (p > 0.05, Mann Whitney U-test). No difference in maximum response to S6c was observed between the two groups; CDM 18.5 +/- 6.19% (n = 15), IHD 10.5 +/- 3.48% (n = 16). No significant alteration in medial ET(B)-receptor density was observed in diseased vessels compared to control, with endothelin-A- (ET(A)) receptors comprising over 90% of the total endothelin (ET) receptor population in both CDM and IHD arteries. Our data imply that there is no increase in the importance of the constrictor ET(B)-receptor in human coronary artery disease.
authors.affiliation: Clinical Pharmacology Unit, University of Cambridge Addenbrooke's Hospital, Centre for Clinical Investigation, UK. jjm1003@medschl.cam.ac.uk
authors.forename: J J
authors.initials: JJ
authors.lastname: Maguire
authors.forename: A P
authors.initials: AP
authors.lastname: Davenport
mesh_terms: D000328:Adult; D001381:Azepines / Q000378:metabolism; D003327:Coronary Disease / Q000378:metabolism*; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology; D019332:Endothelin-1 / Q000494:pharmacology; D005260:Female; D006801:Humans; D007211:Indoles / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000032:analysis* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D001381:Azepines; D019332:Endothelin-1; D007211:Indoles; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; C079574:FR 139317