[ARG(8)]VASOPRESSIN-INDUCED RESPONSES OF THE HUMAN ISOLATED CORONARY-ARTERY - EFFECTS OF NONPEPTIDE RECEPTOR ANTAGONISTS

Contractions induced by [Arg(8)]vasopressin (vasopressin) and the effe ct of nonpeptide vasopressin receptor antagonists were studied in the human isolated coronary artery. Vasopressin induced contraction of cor onary 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 remo val of the endothelium. Contraction was antagonized by the vasopressin V-1 receptor antagonist SR 49059 ((2S) 1-[(2R 3S)-5-chloro-3-(2-chlor ophenyl)-1-(3, o-1H-indole-2-carbonyl]-pyrrolidine-2-carboxamide) (pA( 2): 9.76). OPC-31260 amino)benzoyl}-2,3,4,5-tetrahydro-1H-benazaepine] : vasopressin V-2 receptor antagonist) and OPC-21268 (1-{1-[4-(3-acety laminopropoxy) nzoyl]-4-piperidyl}-3,4-dihydro-2(1H)-quinolinone: repo rted vasopressin V-2 receptor antagonist) were less potent antagonists of vasopressin-induced contractions (pA(2): 7.31 and 5.6, respectivel y). The antagonist potency order (SR 49059 > OPC-31260 > OPC-21268) co rresponds to the reported affinity order for the human cloned vasopres sin V-1 receptor. Therefore, the vasopressin V-1 receptor antagonist S R 49059, but not OPC-21268, appears to be an appropriate tool to inves tigate further the role of vasopressin in pathological processes invol ving coronary vasoconstriction in humans.