Effect of an inducible nitric oxide synthase inhibitor on differential Flow-exhaled nitric oxide in asthmatic patients and healthy volunteers
Effect of an inducible nitric oxide synthase inhibitor on differential Flow-exhaled nitric oxide in asthmatic patients and healthy volunteers
复制标题
DOI：
10.1378/chest.06-3046
复制
发表时间：
2007-08-01
期刊：
影响因子：
9.6
通讯作者：
Viaritonov, Sergei A.
中科院分区：
文献类型：
--
作者：
Brindicci, Caterina;Ito, Ktzuhiro;Viaritonov, Sergei A.
一氧化氮(NO)由呼吸道内的多种细胞，特别是呼吸道上皮细胞产生，哮喘时其浓度升高可能源于炎症呼吸道中表达的诱导型一氧化氮合酶(INOS)。为了评估大气道中产生的NO的支气管流量(即，气道壁NO流量UNO]是否由酶的过度表达引起，我们在哮喘和健康受试者中以双盲、安慰剂对照的方式雾化给予相对选择性的iNOS抑制剂氨基胍，还观察了相同浓度的抑制剂是否对外周肺产生的NO，即肺泡NO浓度[Calv]，单位为百万分之[ppb])或NO在呼吸道的扩散能力(单位为皮升/秒(-1)/ppb(-1))有任何影响。在8名健康受试者和8名哮喘患者中，与生理盐水对照组相比，氨基鸟苷组的JNO显著降低，但两组的CALV和ONO均无明显变化。两组均未观察到血压升高、FEV1下降或不良反应。这些结果表明，哮喘患者大气道中的iNOS是大气道源性NO升高的主要来源，外周肺呼出的NO不受雾化吸入的iNOS的影响。
Nitric oxide (NO) is produced by a variety of cells within the respiratory tract, particularly airway epithelial cells, and its increased concentration in asthma is likely to derive from inducible NO synthase (iNOS) expressed in inflamed airways. To evaluate whether an increased bronchial flux of NO (ie, airway wall NO flux UNO] in picoliters per second) produced in the large airways is due to an enzyme overexpression, we administered a relatively selective iNOS inhibitor, aminoguanidine, by nebulization in a double-blind, placebo-controlled manner in asthmatic and healthy subjects and also investigated whether the same concentration of inhibitor has any effect on NO produced in the peripheral lungs ie, alveolar NO concentration [CALV] in parts per billion [ppb]) or on the diffusing capacity of NO (ONO) [in picoliters per second(-1) per ppb(-1)) in the airways. Aminoguanidine administration resulted in a significant reduction in JNO compared with administration of the saline solution control in eight healthy subjects and in eight patients with asthma but caused no significant changes in CALv or in ONO in either group. No rise in BP, fall in FEV1 or adverse effects were observed in either group. These results indicate that iNOS from larger airways is the predominant source of elevated large airway-derived NO in patients with asthma, and that exhaled NO from peripheral lungs is not affected by a nebulized iNOS.