| Summary: | 碩士 === 慈濟大學 === 整合生理暨臨床科學研究所 === 96 === Long term exposure to intermittent hypoxia (IH), such as occurring in association with obstructive sleep apnea (OSA), may evoke reflex excitation of cardiopulmonary system and even generate systemic inflammation. Pulmonary C-fiber afferents, a major type of lung vagal sensory receptors, are known to be sensitive to chemical mediators stimuli. IH can cause increased release of various chemical mediators (e.g. reactive oxygen species (ROS), and cyclooxygenase products), many of which have been shown to be able to stimulate or sensitize pulmonary C fibers (PCFs) and further eliciting respiratory reflexes. Clinically, OSA may occur concomitantly with noturnal asthma and cough reflex, it is likely that involves a remarkable plasticity of PCFs during airway inflammation. Our laboratory previously demonstrated that, ten episodes of acute IH produced a stimulation, long-term facilitation (LTF) and hypersensitivity of PCFs in rats. Therefore, the present study investigate whether the reactive ROS or/and cyclooxygenase products are involved in IH-induced these PCF alternations. In this study, we carried out using the single-fiber recording technique to determine the characteristics of PCF responses following IH challenge and to investigate the mechanisms possibly underlying these effects. Ten episodes (30 s of 100% N2 + 30 s of room air) of IH were delivered via the respirator into the lungs, and afferent activity of PCFs was recorded in anesthetized, paralyzed, and artificially ventilated rats. In a separate group, we measured the sensitivity of PCFs to both mechanical (lung inflation) and chemical (capsaicin injection) stimuli before and after IH challenge. Pretreatment with vehicle, IH evoked stimulation, LTF, and hypersensitivity to capsaicin of PCFs in rats; the characteristics of the C-fiber responses in the present study were consistent with those of IH alone reported previously. Furthermore, our results show that the C-fiber responses to IH were largely attenuated by pretreatment with dimethylthiourea (DMTU; a hydroxyl redical scavenger) alone, indomethacin (Indo; a cyclooxygenase inhibitor) alone, or a combination of the two. Moreover, pretreatment with DMTU+Indo revealed a pattern of inhibitory response on PCFs similar to that of DMTU alone or Indo alone. In addition, IH challenge produced a higher level of prostaglandin E2, a cyclooxygenase product, in the bronchoalveolar lavage fluid. These results suggest that ten cycles of IH challenge evoked stimulation, LTF, and hypersensitivity of PCFs, all of which are mediated at least partly through hydroxyl radical and cyclooxygenase products.
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