Exhaled nitric oxide production by nitric oxide synthase-deficient mice.
Exhaled nitric oxide production by nitric oxide synthase-deficient mice.
复制标题
一氧化氮合酶缺陷小鼠呼出的一氧化氮的产生。
DOI：
10.1164/ajrccm.162.4.9909037
复制
发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Zapol,WM
中科院分区：
文献类型：
--
作者：
Steudel,W;Kirmse,M;Weimann,J;Ullrich,R;Hromi,J;Zapol,WM
一氧化氮（NO）产生于鼻腔、气道和肺部，由正常动物和人类呼出。尽管气道炎症中呼出NO浓度的增加与气道一氧化氮合酶2 （NOS 2）表达的增加有关，但尚不确定哪种NOS异构体与呼出NO的基线水平有关。因此，我们研究了野生型小鼠和先天缺乏NOS 1、NOS 2或NOS 3的小鼠。通过研究一个封闭的房间，收集一组小鼠呼出的气体，测量气态NO的产生率。野生型小鼠呼出362±35 × 10−15mol g−1min−1NO（平均值±SE， n = 16组，共5只小鼠），NOS 1缺陷小鼠呼出592±74 × 10−15mol g−1min−1NO (n = 15组，与野生型和NOS 2缺陷小鼠相比p < 0.05)， NOS 2缺陷小鼠呼出330±74 × 10−15mol g−1min−1NO （n = 14组），NOS 3缺陷小鼠呼出766±101 × 10−15mol g−1min−1NO （n = 16组，与野生型和NOS 2缺陷小鼠相比p < 0.001）。l- name对NOS的药理抑制作用降低了野生型和NOS 3缺失小鼠的呼出NO产率（p < 0.05），而对NOS 2缺失小鼠无显著影响。l-精氨酸增加了除NOS 2缺陷小鼠外的所有小鼠呼出一氧化氮的产生率。一氧化氮1或一氧化氮3的缺乏与小鼠呼出一氧化氮产量增加有关。由于NOS 2缺陷小鼠是唯一缺乏底物和抑制剂调节的NO呼出变化的基因型，我们认为NOS 2是健康小鼠呼出NO的重要异构体。
Nitric oxide (NO) is produced in the nasal cavities, airways, and lungs and is exhaled by normal animals and humans. Although increased exhaled NO concentrations in airway inflammation have been associated with increased airway expression of nitric oxide synthase 2 (NOS 2), it is uncertain which NOS isoform is responsible for baseline levels of exhaled NO. We therefore studied wild-type mice and mice with a congenital deficiency of NOS 1, NOS 2, or NOS 3. By studying a closed chamber in which the exhaled gas of a group of mice was collected, gaseous NO production rates were measured. Wild-type mice exhaled 362 ± 35 × 10−15mol g−1min−1NO (mean ± SE, n = 16 groups of five mice), NOS 1-deficient mice exhaled 592 ± 74 × 10−15mol g−1min−1NO (n = 15 groups, p < 0.05 versus wild-type and NOS 2-deficient mice), NOS 2-deficient mice 330 ± 74 × 10−15mol g−1min−1NO (n = 14 groups) and NOS 3-deficient mice 766 ± 101 × 10−15mol g−1min−1NO (n = 16 groups, p < 0.001 versus wild-type and NOS 2-deficient mice). Pharmacological NOS inhibition withl-NAME decreased (p < 0.05) the exhaled NO production rate of wild-type and NOS 3-deficient but not of NOS 2-deficient mice.l-Arginine administration increased exhaled NO production rate in all but NOS 2-deficient mice. Absence of NOS 1 or 3 is associated with increased murine exhaled NO production rates. Since NOS 2-deficient mice were the only genotype to lack substrate- and inhibitor-regulated changes of NO exhalation, we suggest that NOS 2 is an important isoform contributing to exhaled NO exhalation in healthy mice.