Nitric oxide-mediated relaxation induced by bradykinin in the isolated mouse trachea.
We examined the nature of the relaxant effect of bradykinin on mouse isolated tracheal rings. Bradykinin produced a concentration-dependent relaxation in mouse tracheal rings contracted by carbachol. Potentiation of the contractile effect of carbachol and inhibition of the relaxant effect of bradykinin by pretreatment with NG-nitro-L-arginine methyl ester (L-NAME), L-glutamine (L-Gln) and methylene blue (MeB) suggested that the peptide activated the L-arginine nitric oxide (NO) pathway. Part of the relaxant effect of bradykinin was also mediated through the release of cyclooxygenase metabolites of arachidonic acid, as evidenced by the inhibition of this response by lysine acetylsalicylic acid (ASA) pretreatment. Bradykinin also caused a relaxant response in precontracted tracheal rings in the presence of lower but not higher concentrations of K+ (> 60 mM). NG-nitro-L-arginine methyl ester and L-Gln did not alter the contractile effect of K+. K+ channel blockers partially inhibited the relaxant effect of bradykinin in carbachol-induced precontracted tracheal rings. Tetraethylammonium, a non-selective blocker of K+ channels, completely abolished the relaxant response to the peptide. Among the other channel blockers, the inhibitory effect of glibenclamide was slightly greater than that of apamine and iberiotoxin, indicating the involvement of K(ATP) channels in the relaxant response to the peptide. These results suggest that the mechanisms of the relaxation induced by bradykinin in carbachol-induced precontracted mouse tracheal muscle primarily involve activation of L-arginine NO and arachidonic acid cyclooxygenase pathways and secondly K+ channels.
Department of Pharmacology, Faculty of Medicine, Gazi University, Beşevler, Ankara, Turkey.
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Sipahi
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ZS
Ercan
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Türker
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D005260:Female; D005998:Glycine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D026902:Potassium Channel Blockers; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
D026902:Potassium Channel Blockers; D009569:Nitric Oxide; D002217:Carbachol; D001241:Aspirin; D001920:Bradykinin; D005998:Glycine; D019331:NG-Nitroarginine Methyl Ester