INDUCTION OF BRADYKININ-B(1) RECEPTOR-MEDIATED RELAXATION IN THE ISOLATED RABBIT CAROTID-ARTERY

Responses to bradykinin and to the bradykinin B1 receptor agonist des- Arg9-bradykinin were studied in freshly isolated rabbit carotid artery rings and in rings after a 5-h period of incubation. In freshly isola ted rings precontracted with noradrenaline, neither bradykinin nor des -Arg9-bradykinin changed the tension whereas acetylcholine relaxed the vessel in a concentration-dependent manner. After incubation, des-Arg 9-bradykinin, and to a lesser extent bradykinin, produced an endotheli um-dependent relaxation. This response was abolished by endothelium re moval, N(omega)-nitro-L-arginine or cycloheximide but was unaffected b y indomethacin. In contrast, the response to acetylcholine was unaffec ted by cycloheximide and was partially inhibited by N(omega)-nitro-L-a rginine. In addition, the relaxation curve for des-Arg9-bradykinin was markedly shifted (44-fold) by the selective bradykinin B1 receptor an tagonist, des-Arg9-[Leu8]bradykinin (3 muM) and was unaffected by the bradykinin B2 receptor antagonist, Hoe 140 (1 muM). We conclude that i n vitro incubation of the rabbit carotid artery induced endothelial br adykinin B1 receptors coupled to the release of endothelium-derived ni tric oxide.