NITRIC OXIDE-MEDIATED RELAXATION INDUCED BY BRADYKININ IN THE ISOLATED MOUSE TRACHEA

We examined the nature of the relaxant effect of bradykinin on mouse i solated tracheal rings. Bradykinin produced a concentration-dependent relaxation in mouse tracheal rings contracted by carbachol. Potentiati on of the contractile effect of carbachol and inhibition of the relaxa nt effect of bradykinin by pretreatment with N-G-nitro-L-arginine meth yl eater (L-NAME), L-glutamine (L-Gln) and methylene blue (MeB) sugges ted that the peptide activated the L-arginine nitric oxide (NO) pathwa y. Part of the relaxant effect of bradykinin was also mediated through the release of cyclooxygenase metabolites of arachidonic acid, as evi denced by the inhibition of this response by lysine acetylsalicylic ac id (ASA) pretreatment. Bradykinin also caused a relaxant response in p recontracted tracheal rings in the presence of lower but not higher co ncentrations of K+ (> 60 mM). N-G-nitro-L-arginine methyl ester and L- Gln did not alter the contractile effect of K+. K+ channel blockers pa rtially inhibited the relaxant effect of bradykinin in carbachol-induc ed precontracted tracheal rings. Tetraethylammonium, a non-selective b locker of K+ channels, completely abolished the relaxant response to t he peptide. Among the other channel blockers, the inhibitory effect of glibenclamide was slightly greater than that of apamine and iberiotox in, indicating the involvement of K-ATP channels in the relaxant respo nse to the peptide. These results suggest that the mechanisms of the r elaxation induced by bradykinin in carbachol-induced precontracted mou se tracheal muscle primarily involve activation of L-arginine NO and a rachidonic acid cyclooxygenase pathways and secondly K+ channels. (C) 1998 Elsevier Science B.V. All rights reserved.