title: Endothelin induces vasoconstriction in the bone vasculature in vitro: an effect mediated by a single receptor population.
abstract: The aim of this study was to define the types of endothelin receptors present in the canine tibial vasculature. Endothelin receptor agonists and antagonists were used in two different models: isolated nutrient tibial arteries in organ bath and in vitro-perfused canine tibial bones. In isolated nutrient tibial arteries, endothelin-1 caused concentration-dependent contractions of rings with and without endothelium. BQ-123, a selective endothelin-A antagonist, induced a significant rightward shift of endothelin-1 concentration-response curves. No contractions were observed with sarafotoxin S6c, a selective endothelin-B agonist. The responses of endothelin-1 were not affected by the presence of NG-monomethyl-L-arginine acetate plus indomethacin or by removal of the endothelium. In perfused tibial bones, endothelin-1 was more potent than endothelin-3 in causing concentration-dependent contractions. Neither endothelin-1, endothelin-3, nor sarafotoxin S6c caused relaxations. Neither the inhibition of nitric oxide nor the inhibition of prostaglandins significantly altered contractions to endothelin-1. These concordant data indicate that endothelin is a vasoconstrictor in the bone vasculature, an effect that appears to be mediated only through endothelin-A receptors.
authors.affiliation: Mayo Graduate School of Medicine, Rochester, Minnesota, USA.
authors.forename: B C
authors.initials: BC
authors.lastname: Coessens
authors.forename: V M
authors.initials: VM
authors.lastname: Miller
authors.forename: M B
authors.initials: MB
authors.lastname: Wood
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001158:Arteries / Q000737:chemistry / Q000187:drug effects; D001842:Bone and Bones / Q000098:blood supply*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009924:Organ Culture Techniques; D017466:Receptors, Endothelin / Q000032:analysis; D012039:Regional Blood Flow / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D019323:omega-N-Methylarginine
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016232:Endothelins; D004791:Enzyme Inhibitors; D017466:Receptors, Endothelin; D019323:omega-N-Methylarginine; D001120:Arginine; D007213:Indomethacin