Abstract
We recently described a sensory nerve inhibitory system that mediates relaxation in the airways of Sprague-Dawley rats. Results of several studies have shown that this system protects the lungs against injury induced by toxic stimuli. Whether a similar inhibitory system exists in the airways of Fischer 344 (F344) rats is unknown. Because this rat strain is used extensively in lung toxicological research, the purpose of this study was to determine whether a sensory nerve inhibitory system exists in intrapulmonary bronchi and tracheae isolated from F344 rats. In intrapulmonary bronchi at resting tone, substance P (1.0 μM) evoked a transient contraction that was inhibited by the 5-HT 2A receptor antagonist, ketanserin. Exposing airway segments to compound 48/80 to degranulate mast cells also abolished substance P-induced contractions. Inhibition of cyclooxygenase with meclofenamate augmented markedly the contraction to substance P in the intrapulmonary bronchi. In intrapulmonary bronchi that were contracted with bethanechol, substance P evoked a biphasic response characterized by an increase in tension above that induced by bethanechol followed by relaxation. Incubation of the airways with ketanserin abolished the contractile portion of the response; relaxation responses were augmented after ketanserin. In contracted intrapulmonary bronchi that had been treated with compound 48/80, substance P and capsaicin caused relaxation responses that were inhibited markedly or were nearly abolished by the NK 1 receptor antagonist, RP67580, by meclofenamate, and by denuding the epithelium. Capsaicin-induced relaxation responses also were abolished by desensitization of C-fibers with capsaicin. Only ketanserin-sensitive contractile responses were observed in response to substance P in tracheal segments. We conclude that a sensory nerve inhibitory system exists in the intrapulmonary airways of F344 rats. The presence of this inhibitory system in F344 rat airways may play a protective role against lung injury induced by inhaled toxicants.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
