SENSORY NERVE-MEDIATED INHIBITORY RESPONSES IN AIRWAYS OF F344 RATS

We recently described a sensory nerve inhibitory system that mediates relaxation in the airways of Sprague-Dawley rats. Results of several s tudies have shown that this system protects the lungs against injury i nduced by toxic stimuli. Whether a similar inhibitory system exists in the airways of Fischer 344 (F344) rats is unknown. Because this rat s train is used extensively in lung toxicological research, the purpose of this study was to determine whether a sensory nerve inhibitory syst em exists in intrapulmonary bronchi and tracheae isolated from F344 ra ts. In intrapulmonary bronchi at resting tone, substance P (1.0 mu M) evoked a transient contraction that was inhibited by the 5-HT2A recept or antagonist, ketanserin. Exposing airway segments to compound 48/80 to degranulate mast cells also abolished substance P-induced contracti ons. Inhibition of cyclooxygenase with meclofenamate augmented markedl y the contraction to substance P in the intrapulmonary bronchi. In int rapulmonary bronchi that were contracted with bethanechol, substance P evoked a biphasic response characterized by an increase in tension ab ove that induced by bethanechol followed by relaxation. Incubation of the airways with ketanserin abolished the contractile portion of the r esponse; relaxation responses were augmented after ketanserin. In cont racted intrapulmonary bronchi that had been treated with compound 48/8 0, substance P and capsaicin caused relaxation responses that were inh ibited markedly or were nearly abolished by the NK1 receptor antagonis t, RP67580, by meclofenamate, and by denuding the epithelium. Capsaici n-induced relaxation responses also were abolished by desensitization of C-fibers with capsaicin. Only ketanserin-sensitive contractile resp onses were observed in response to substance P in tracheal segments. W e conclude that a sensory nerve inhibitory system exists in the intrap ulmonary airways of F344 rats. The presence of this inhibitory system in F344 rat airways may play a protective role against lung injury ind uced by inhaled toxicants. (C) 1997 Elsevier Science Ireland Ltd.