[Arg 8]Vasopressin-induced responses of the human isolated coronary artery: effects of non-peptide receptor antagonists

Contractions induced by [Arg 8]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 pD 2 (9.25) but a low E max (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 V 1 receptor antagonist SR 49059 ((2 S) 1-[(2 R 3 S)-5-chloro-3-(2-chlorophenyl)-1-(3,4-dimethoxybenzene-sulfonyl)-3-hydroxy-2,3-dihydro-1 H-indole-2-carbonyl]-pyrrolidine-2-carboxam (pA 2: 9.76). OPC-31260 ([5-dimethylamino-1-{4-(2-methylbenzoylamino)benzoyl}-2,3,4,5-tetrahydro-1 H-benzazepine]: vasopressin V 2 receptor antagonist) and OPC-21268 (1-1-[4-(3-acetylaminopropoxy) benzoyl]-4-piperidyl-3,4-dihydro-2(1 H)-quinolinone: reported vasopressin V 1 receptor antagonist) were less potent antagonists of vasopressin-induced contractions (pA 2: 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 V 1 receptor. Therefore, the vasopressin V 1 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.