Involvement of bradykinin B1 and B2 receptors in relaxation of mouse isolated trachea

The aim of the present study was to investigate the effects of bradykinin and [des‐Arg9]‐bradykinin and their relaxant mechanisms in the mouse isolated trachea. In the resting tracheal preparations with intact epithelium, bradykinin and [des‐Arg9]‐bradykinin (each drug, 0.01–10 μm) induced neither contraction nor relaxation. In contrast, bradykinin (0.01–10 μm) induced concentration‐dependent relaxation when the tracheal preparations were precontracted with methacholine (1 μm). The relaxation induced by bradykinin was inhibited by the B2 receptor antagonist, d‐Arg0‐[Hyp3,Thi5,d‐Tic7,Oic8]‐bradykinin (Hoe 140, 0.01–1 μm) in a concentration‐dependent manner whereas the B1 receptor antagonist, [des‐Arg9,Leu8]‐bradykinin (0.01–1 μm), had no inhibitory effect on bradykinin‐induced relaxation. [des‐Arg9]‐bradykinin (0.01–10 μm) also caused concentration‐dependent relaxation after precontraction with methacholine. The relaxation induced by [des‐Arg9]‐bradykinin was concentration‐dependently inhibited by the B1 receptor antagonist, [des‐Arg9,Leu8]‐bradykinin (0.01–1 μm), whereas the B2 receptor antagonist, Hoe 140 (0.01–1 μm) was without effect. In the presence of the cyclo‐oxygenase inhibitor, indomethacin (0.01–1 μm), the relaxations induced by bradykinin and [des‐Arg9]‐bradykinin were inhibited concentration‐dependently. Two nitric oxide (NO) biosynthesis inhibitors NG‐nitro‐l‐arginine methyl ester (l‐NAME, 100 μm) and NG‐nitro‐l‐arginine (l‐NOARG, 100 μm) had no inhibitory effects on the relaxations induced by bradykinin and [des‐Arg9]‐bradykinin. Neither did the selective inhibitor of the soluble guanylate cyclase, 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ, 10 μm) inhibit the relaxations induced by bradykinin and [des‐Arg9]‐bradykinin. Prostaglandin E2 (PGE2, 0.01–33 μm) caused concentration‐dependent relaxation of the tracheal preparations precontracted with methacholine. Indomethacin (1 μm) and ODQ (10 μm) exerted no inhibitory effects on the relaxation induced by PGE2. The NO‐donor, sodium nitroprusside (SNP; 0.01–100 μm) also caused concentration‐dependent relaxation of the tracheal preparations precontracted with methacholine. ODQ (0.1–1 μm) concentration‐dependently inhibited the relaxation induced by SNP. These data demonstrate that bradykinin and [des‐Arg9]‐bradykinin relax the mouse trachea precontracted with methacholine by the activation of bradykinin B2‐receptors and B1‐receptors, respectively. The stimulation of bradykinin receptors induce