In vitro hypoxia and levcromakalim relax rat pulmonary artery by a common mechanism

Abstract

The actions of bradykinin and its metabolite des-Arg9 bradykinin are mediated through activation of bradykinin B2 and B1 receptors, respectively. The aim of the present study was to characterize native bradykinin receptors focusing on induction and desensitization using rat isolated vas deferens. Tissues were mounted in organ baths for isometric recordings and neurogenically mediated contractions were evoked by electrical stimulation. Des-Arg9 bradykinin enhanced the magnitude of the electrically evoked contractions and this effect (which was sensitive to blockade by the peptide bradykinin B1 receptor selective antagonist B9858, Lys-Lys-(Hyp3,Cpg5,D-Tic7,Cpg8)des-Arg9 bradykinin) was only observed following a pre-incubation period and was greatest following 5 h of pre-incubation. Bradykinin also potentiated neurogenically evoked contractions and this effect was sensitive to blockade by Hoe 140 (D-Arg(Hyp3,Thi5,D-Tic7,Oic8)bradykinin, a peptide bradykinin B2 receptor antagonist) and was present without pre-incubation but was increased by pre-incubation and reached maximum at the 5-h incubation time point. Responses to bradykinin were larger than those to des-Arg9 bradykinin. Bradykinin responses did not show desensitization on repeated agonist stimulation. These data confirm in rat isolated vas deferens bradykinin B2, but not B1, receptors are constitutively expressed, that both receptor populations are inducible and B2 receptors do not exhibit desensitization.