Leukotrienes mediate tracheal hyperresponsiveness after nitric oxide synthesis inhibition.
Preincubation of guinea pig tracheas with the nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME, 120 microM) resulted in a significant upward shift of the histamine concentration-response curve with a concomitant inhibition of prostaglandin E2 production. Preincubation of the preparations with a 5-lipoxygenase inhibitor (AA-861, 2-(12-hydroxy-5,10-dodecadiynyl)-3,5,6-trimethyl-p-benzoquinone) or a leukotriene C4,D4,E4 receptor antagonist (FPL 55712, sodium 7-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxy propoxy]-4-oxo-8- propyl-4H-1-benzopyran-2-carboxylate) totally blocked the L-NAME-induced tracheal hyperresponsiveness. A shift from cyclo-oxygenase to lipoxygenase products, in particular leukotrienes, is likely to be responsible for the L-NAME-induced tracheal hyperresponsiveness.
Folkerts
G
G
Department of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Netherlands.
Van der Linde
H
H
Van de Loo
P G
PG
Engels
F
F
Nijkamp
F P
FP
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016227:Benzoquinones / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D015289:Leukotrienes / Q000502:physiology*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D014132:Trachea / Q000187:drug effects / Q000502:physiology*
D016227:Benzoquinones; D002867:Chromones; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D009569:Nitric Oxide; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; C006312:FPL 55712; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester