title: Functional role of endothelin ETA and ETB receptors in venous and arterial smooth muscle.
abstract: The functional importance of endothelin ETA and ETB receptors in selected arterial and venous smooth muscle preparations was characterized. Endothelin-1 induced force in the saphenous and jugular veins is normally mediated by endothelin ETB-like receptors. However, desensitization or pharmacological block of these receptors reveals an endothelin ETA receptor population that is of sufficient size to mediate full endothelin-1-evoked force. Block of either endothelin ETA or endothelin ETB receptors alone is insufficient to antagonize endothelin-1-evoked force in saphenous vein. Endothelin-1-induced force in hamster aorta may also be mediated by activation of both endothelin ETA and ETB receptors. However, activation of endothelin ETB-like receptors alone is insufficient to generate a full endothelin-1 response. Sarafotoxin S6c treatment, to desensitize endothelin ETB receptors, failed to affect the responses of rat aorta and rabbit carotid artery to endothelin-1 or endothelin ETA receptor antagonists. These findings indicate that selective endothelin receptor antagonists will vary enormously in their efficacy against endothelin-induced force in different vascular beds.
authors.affiliation: Department of Pharmacology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000, USA.
authors.forename: N J
authors.initials: NJ
authors.lastname: Lodge
authors.forename: R
authors.initials: R
authors.lastname: Zhang
authors.forename: N N
authors.initials: NN
authors.lastname: Halaka
authors.forename: S
authors.initials: S
authors.lastname: Moreland
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000494:pharmacology*; D007601:Jugular Veins / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D017466:Receptors, Endothelin / Q000502:physiology*; D012501:Saphenous Vein / Q000187:drug effects / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014757:Viper Venoms / Q000494:pharmacology*
chemical_list: D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6