Mhanna Maroun J, Haxhiu Musa A, Jaber Marwan A, Walenga Ronald W, Chang Chang-Ho, Liu Shijian, Martin Richard J
Department of Pediatrics, MetroHealth Medical Center, 2500 MetroHealth Dr., Cleveland, OH 44109, USA.
J Appl Physiol (1985). 2004 May;96(5):1854-60. doi: 10.1152/japplphysiol.01178.2002. Epub 2004 Feb 6.
Hyperoxic exposure enhances airway reactivity in newborn animals, possibly due to altered relaxation. We sought to define the role of prostaglandinand nitric oxide-mediated mechanisms in impaired airway relaxation induced by hyperoxic stress. We exposed 7-day-old rat pups to either room air or hyperoxia (>95% O2) for 7 days to assess airway relaxation and cAMP and cGMP production after electrical field stimulation (EFS). EFS-induced relaxation of preconstricted trachea was diminished in hyperoxic vs. normoxic animals (P < 0.05). Indomethacin (a cyclooxygenase inhibitor) reduced EFS-induced airway relaxation in tracheae from normoxic (P < 0.05), but not hyperoxic, rat pups; however, in the presence of NG-nitro-L-arginine methyl ester (a nitric oxide synthase inhibitor) EFS-induced airway relaxation was similarly decreased in tracheae from both normoxic and hyperoxic animals. After EFS, the increase from baseline in the production of cAMP was significantly higher in tracheae from normoxic than hyperoxic rat pups, and this was accompanied by greater prostaglandin E2 release only in the normoxic group. cGMP production after EFS stimulation did not differ between normoxic and hyperoxic groups. We conclude that hyperoxia impairs airway relaxation in immature animals via a mechanism primarily involving the prostaglandin-cAMP signaling pathway with an impairment of prostaglandin E2 release and cAMP accumulation.
高氧暴露会增强新生动物的气道反应性，这可能是由于舒张功能改变所致。我们试图确定前列腺素和一氧化氮介导的机制在高氧应激诱导的气道舒张受损中的作用。我们将7日龄的大鼠幼崽暴露于室内空气或高氧环境（>95% O2）中7天，以评估电场刺激（EFS）后气道舒张以及环磷酸腺苷（cAMP）和环磷酸鸟苷（cGMP）的产生。与常氧动物相比，高氧环境下的动物中，EFS诱导的预收缩气管舒张减弱（P < 0.05）。吲哚美辛（一种环氧化酶抑制剂）可降低常氧大鼠幼崽气管中EFS诱导的气道舒张（P < 0.05），但对高氧大鼠幼崽无效；然而，在存在NG-硝基-L-精氨酸甲酯（一种一氧化氮合酶抑制剂）的情况下，常氧和高氧动物气管中EFS诱导的气道舒张均同样降低。EFS后，常氧大鼠幼崽气管中cAMP产量相对于基线的增加显著高于高氧大鼠幼崽，且仅在常氧组中伴有更高的前列腺素E2释放。EFS刺激后，常氧组和高氧组之间cGMP的产生没有差异。我们得出结论，高氧通过主要涉及前列腺素-cAMP信号通路的机制损害未成熟动物的气道舒张，其中前列腺素E2释放和cAMP积累受损。
