Roles of nitric oxide and neuropeptides in the development of lung injuries induced by chemical irritants.

通过吸入实验，研究神经肽和一氧化氮在大鼠或小鼠对臭氧的呼吸道反应中的作用。1.神经肽的作用本研究的目的是确定速激肽是否介导C纤维对臭氧(O_3)暴露的保护作用。雄性SD大鼠暴露于1ppmO_3或空气中3小时。2小时后测定吸入乙酰甲胆碱后的气道反应性，并进行支气管肺泡灌洗(BAL)。用选择性NK_1和NK_2受体拮抗剂在O_3暴露和乙酰甲胆碱攻击期间或在乙酰甲胆碱攻击前进行治疗。此外，我们还观察了去除C纤维的辣椒素对臭氧诱导的BAL细胞和蛋白变化的影响。O_3暴露大鼠经拮抗剂处理后，中性粒细胞进入肺和呼吸道的数量明显增加，上皮细胞脱落明显增多。…对大鼠的预处理作用O_3暴露后增加拮抗剂对BAL细胞的恢复无影响。两种治疗方法对基础肺力学或呼吸道反应性均无影响。新生儿辣椒素预处理。与溶媒组相比，O_3组大鼠BAL中性粒细胞和蛋白质也明显增加。这些结果表明速激肽介导了C纤维对O_3诱导的肺损伤的保护作用，但不参与减轻气道高反应性的发展。2.一氧化氮的作用本研究的目的是探讨一氧化氮是否介导了对O_3的气道反应。24小时后行支气管肺泡灌洗(BAL)。O_3/NOARG组BAL液中中性粒细胞减少，提示NO可能参与了O_3诱导的气道炎症的发生。我们进一步评估了一氧化氮在O_3诱导的气道高反应性中的作用，但没有观察到明显的联系。较少

Inhalation studies were performed to examine roles of neuropeptides and nitric oxide in airway responses to ozone in rats or mice.1.Role of neuropeptidesThe purpose of this study was to determine whether tachykinins mediate the protective effects of C-fibers against ozone (O_3) exposure. Male Sprague-Dawley rats were exposed to 1ppm O_3 or air for three hours. Two hours later airway responsiveness to inhaled methacholine was measured and a bronchoalveolar lavage (BAL) was performed. Rats were treated with the selective NK_1 and NK_2 receptor antagonist, either throughout the O_3 exposure and methacholine challenge or just before the methacholine challenge. The effect of neonatal capsaicin pretreatment, which ablates C-fibers, on O_3-induced changes in BAL cells and protein was also examined. Pretreatment of rats with the antagonists during O_3 exposure significantly augmented influx of neutrophils into the lung and airways and shedding of epithelial cells. Pretreatment of rats with the … More antagonists after the O_3 exposure had no effect on BAL cell recovery. Neither treatment had any effect on baseline pulmonary mechanics or airway responsiveness. Neonatal capsaicin pretreatment. which ablates C-fibers, also resulted in increased BAL neutrophils and protein after O_3 compared to vehicle treated rats. These results suggest that tachykinins mediate protective effects of C fibers against O_3-induced lung injury, but are not involved in attenuating the development of airway hyperresponsiveness.2.Role of nitric oxideThe purpose of this study was to examine whether nitric oxide mediate airway responses to O_3. Male ICR mice with/without N-Nitro-Arginine (NOARG,100mg/kg) were exposed to 1ppm O_3 or air for four hours. Twenty-four hours later a bronchoalveolar lavage (BAL) was performed. Number of neutrophils in BAL fluid was decreased in the O_3/NOARG group, which indicated nitric oxide might relate to development of O_3 induced-airway inflammation. We further evaluated the role of nitric oxide in O_3-induced airway hyperresponsiveness, but no clear relationship was observed. Less