The bradykinin B2 receptor antagonist WIN 64338 inhibits the effect of des-Arg9-bradykinin in endothelial cells

Abstract

WIN 64338 (phosphonium, [[4-[[2-[[bis(cyclohexylamino) methylene] amino]-3-(2-naphthalenyl) 1-oxopropyl]amino]-phenyl]- tributyl, chloride, monohydrochloride) is the first potent nonpeptide competitive bradykinin B2 receptor antagonist as shown in classical pharmacological preparations with no activity in the rabbit aorta stimulated by the bradykinin B1 receptor agonist des-Arg9-bradykinin. In primary cultured bovine aortic endothelial cells, both bradykinin and des-Arg9-bradykinin stimulate the production of intracellular cyclic GMP, an index for the production of nitric oxide. Surprisingly, WIN 64338 did not inhibit bradykinin but abolished the effect of des-Arg9-bradykinin suggesting that kinin receptor antagonists do not necessarily discriminate between kinin receptor subtypes in an identical way in different tissues and species.