Low-dose carbon monoxide reduces airway hyperresponsiveness in mice
Low-dose carbon monoxide reduces airway hyperresponsiveness in mice
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DOI：
10.1152/ajplung.00145.2003
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发表时间：
2003-12-01
影响因子：
4.9
通讯作者：
Choi, AMK
中科院分区：
文献类型：
--
作者：
Ameredes, BT;Otterbein, LE;Choi, AMK
呼出气体中的一氧化碳（CO）已被证明在哮喘中升高;然而，其功能尚不清楚，并且有一些潜在的支气管保护作用，以降低气道高反应性（AHR）。因此，CO逆转乙酰甲胆碱（MCh）诱导的支气管收缩的能力进行了评估，在C57 BL/6（C57）和A/J小鼠有和没有由卵清蛋白（OVA）产生的气道炎症。急性给予CO（1%空气，10分钟）可使OVA攻击的C57小鼠中由MCh驱动的肺阻力增加平均减少50%（从14.5到7.1 cmH（2）O。ml（-1）。s（-1）），而在未处理的C57小鼠或单独吸入空气的OVA攻击的C57小鼠中没有观察到影响。急性吸入CO（500 ppm = 0.05%，持续10分钟）可使气道高反应性A/J小鼠中MCH诱导的气道反应性（AR）降低20 - 60%，而在5天内重复10分钟给予500 ppm CO可使AR降低50%。重复给予低剂量CO [250（0.025%）及（0.05%）500 ppm，1小时/天，5天]给予具有气道炎症的A/J小鼠，与未接受CO的小鼠相比，同样导致AR下降50%。3-a]喹喔啉-1-酮或竞争性抑制剂8-溴-cGMP的Rp非对映体可抑制CO对AHR的作用，提示CO的作用是通过这一机制介导的。这些结果表明，低剂量CO可以有效地逆转AHR在存在和不存在气道炎症的小鼠，并建议在调制AHR的CO的潜在作用。
Carbon monoxide (CO) in expired gas has been shown to be elevated with asthma; however, its function is not known, and there is some potential that it may serve a bronchoprotective role to decrease airway hyperresponsiveness (AHR). Thus the ability of CO to reverse methacholine (MCh)-induced bronchoconstriction was evaluated in C57BL/6 (C57) and A/J mice with and without airway inflammation produced by ovalbumin ( OVA). Acutely administered CO (1% in air, 10 min) reduced MCh-driven increases in lung resistance in OVA-challenged C57 mice by an average of 50% (from 14.5 to 7.1 cmH(2)O . ml(-1) . s(-1)), whereas no effect was observed in naive C57 mice or OVA-challenged C57 mice inhaling air alone. Acutely inhaled CO (500 ppm = 0.05%, for 10 min) reduced MCh-induced airway reactivity (AR) by 20 - 60% in airway hyperresponsive naive A/J mice, whereas repeated 10-min administrations of 500 ppm CO over a 5-day period decreased AR by 50%. Repeated administration of low-dose CO [250 (0.025%) and (0.05%) 500 ppm, 1 h/day, 5 days] to A/J mice with airway inflammation likewise resulted in a drop of AR by 50%, compared with those not receiving CO. Inhibition of guanylyl cyclase/guanosine 3', 5'-cyclic monophosphothioate (cGMP) using 1H-[1,2,4] oxydiazolo[ 4,3-a] quinoxalin-1-one or a competitive inhibitor, Rp diastereomers of 8-bromo-cGMP, resulted in inhibition of the effect of CO on AHR, suggesting that the effects of CO were mediated through this mechanism. These results indicate that low-dose CO can effectively reverse AHR in the presence and absence of airway inflammation in mice and suggest a potential role for CO in the modulation of AHR.