title: [Arg8]vasopressin-induced responses of the human isolated coronary artery: effects of non-peptide receptor antagonists.
abstract: Contractions induced by [Arg8]vasopressin (vasopressin) and the effect of nonpeptide vasopressin receptor antagonists were studied in the human isolated coronary artery. Vasopressin induced contraction of coronary artery segments with a high pD2 (9.25) but a low Emax (11.8% of the response to 100 mM K+). This response was not affected by removal of the endothelium. Contraction was antagonized by the vasopressin V1 receptor antagonist SR 49059 ((2S) 1-[(2R 3S)-5-chloro-3-(2-chlorophenyl)-1-(3,4-dimethoxybenzene- sulfonyl)-3-hydroxy-2,3-dihydro-1H-indole-2-carbonyl]-pyrrolidine-2- carboxamide) (pA2: 9.76). OPC-31260 ([5-dimethylamino-1-(4-(2-methylbenzoylamino)benzoyl)-2,3,4,5-tetr ahydro-1H- benzazepine]: vasopressin V2 receptor antagonist) and OPC-21268 (1-(1-[4-(3-acetylaminopropoxy) benzoyl]-4-piperidyl)-3,4- dihydro-2(1H)-quinolinone: reported vasopressin V1 receptor antagonist) were less potent antagonists of vasopressin-induced contractions (pA2: 7.31 and 5.6, respectively). The antagonist potency order (SR 49059 > OPC-31260 > OPC-21268) corresponds to the reported affinity order for the human cloned vasopressin V1 receptor. Therefore, the vasopressin V1 receptor antagonist SR 49059, but not OPC-21268, appears to be an appropriate tool to investigate further the role of vasopressin in pathological processes involving coronary vasoconstriction in humans.
authors.affiliation: Department of Pharmacology, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, Netherlands.
authors.forename: W A
authors.initials: WA
authors.lastname: Bax
authors.forename: P H
authors.initials: PH
authors.lastname: Van der Graaf
authors.forename: W B
authors.initials: WB
authors.lastname: Stam
authors.forename: E
authors.initials: E
authors.lastname: Bos
authors.forename: D
authors.initials: D
authors.lastname: Nisato
authors.forename: P R
authors.initials: PR
authors.lastname: Saxena
mesh_terms: D000293:Adolescent; D000328:Adult; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology; D002648:Child; D003331:Coronary Vessels / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D007211:Indoles; D010880:Piperidines; D011759:Pyrrolidines; D015363:Quinolones; D014662:Vasoconstrictor Agents; D001127:Arginine Vasopressin; C068644:OPC 21268; C076251:mozavaptan; C082134:relcovaptan; D011188:Potassium