title: Functional comparison of endothelin receptors in human and rat pulmonary artery smooth muscle.
abstract: The receptors mediating arterial smooth muscle contraction to endothelins (ET) differ among species and origin of vascular bed. We characterized ET receptors mediating contraction of endothelium-denuded human intralobar pulmonary artery (hIPA) and rat intralobar (rIPA) and extralobar left branch (rLPA) pulmonary artery with ET-1, ET-2, ET-3, sarafotoxin S6c, sarafotoxin S6b, and ET receptor antagonists in vitro. Rat aorta was studied for comparison. Each vascular segment showed concentration-dependent contraction with a rank order sensitivity (pD2) profile of ET-1 > or = ET-2 = sarafotoxin S6b > ET-3. Maximum contraction to ET-1 was greater than to sarafotoxin S6c in all preparations. Responses of rIPA and rLPA to sarafotoxin S6c were conspicuous when compared with hIPA or aorta. The ET(A) receptor blockers BQ-123 and BMS-182874 competitively antagonized ET-1 responses of hIPA and aorta, but not rLPA. The ET(B) receptor antagonist BQ-788 attenuated contractions of rIPA and rLPA to ET-3 and sarafotoxin S6c, respectively. In conclusion, ET(B)-mediated contraction of endothelium-denuded conduit pulmonary arteries varies among species and may contribute more to contraction of rIPA and rLPA than of hIPA and aorta, although maximum ET(B)-mediated contraction is smaller than that mediated by the ET(A) receptor.
authors.affiliation: Respiratory, Inflammatory, and Neurological Diseases Research Section, ZENECA Pharmaceuticals, Wilmington, Delaware 19850-5437, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Bialecki
authors.forename: C S
authors.initials: CS
authors.lastname: Fisher
authors.forename: W W
authors.initials: WW
authors.lastname: Murdoch
authors.forename: H G
authors.initials: HG
authors.lastname: Barthlow
authors.forename: D L
authors.initials: DL
authors.lastname: Bertelsen
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D003619:Dansyl Compounds / Q000494:pharmacology; D065128:Endothelin Receptor Antagonists; D006801:Humans; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism*; D051381:Rats / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D017466:Receptors, Endothelin / Q000378:metabolism*
chemical_list: D003619:Dansyl Compounds; D065128:Endothelin Receptor Antagonists; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D017466:Receptors, Endothelin; C085754:5-(dimethylamino)-N-(3,4-dimethyl-5-isoxazolyl)-1-naphthalenesulfonamide; C086539:BQ 788; C072247:cyclo(Trp-Asp-Pro-Val-Leu)