Congenital NOS2 deficiency prevents impairment of hypoxic pulmonary vasoconstriction in murine ventilator-induced lung injury.
Congenital NOS2 deficiency prevents impairment of hypoxic pulmonary vasoconstriction in murine ventilator-induced lung injury.
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DOI：
10.1152/ajplung.00396.2006
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发表时间：
2007-11
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通讯作者：
Rong Liu;Y. Hotta;A. Graveline;O. V. Evgenov;Emmanuel S. Buys;K. Bloch;F. Ichinose;W. Zapol
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文献类型：
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作者：
Rong Liu;Y. Hotta;A. Graveline;O. V. Evgenov;Emmanuel S. Buys;K. Bloch;F. Ichinose;W. Zapol
低通气性肺血管收缩（HPV）通过将血流从通气不良的肺区域转移开来维持肺损伤期间的全身动脉氧合。呼吸机诱导的肺损伤（VILI）的特征是肺部炎症、肺水肿和HPV受损，导致全身性低氧血症。通过研究诱导型一氧化氮合酶（NOS 2）先天缺陷小鼠和用选择性NOS 2抑制剂L-N（6）-（1-亚氨基乙基）赖氨酸（L-NIL）治疗的野生型小鼠，我们研究了NOS 2对接受6 h高潮气量（HV（T））或低潮气量（LV（T））通气的麻醉小鼠中HPV损伤的作用。通过测量左主支气管阻塞（LMBO）后左肺血管阻力（LPVR）的变化来评估HPV。LMBO增加野生型、NOS 2（-/-）和野生型小鼠的LPVR相似（分别为96% +/-30%、103% +/-33%和80% +/-16%，平均值+/- SD），这些小鼠在开始LV（T）通气前30分钟用L-NIL处理。在HV（T）通气6小时的野生型小鼠中，HPV受损（23% +/- 16%）。相比之下，在开始HV（T）通气前30分钟或开始HV（T）通气后6小时用L-NIL处理的NOS 2（-/-）和野生型小鼠中，HV（T）通气6小时后HPV得以保留（分别为66% +/-22%、82% +/-29%和85% +/-16%）。在HV（T）通气和LMBO 6小时后，NOS 2（-/-）小鼠的全身动脉氧分压高于野生型小鼠（192 +/- 11 vs. 171 +/- 17 mmHg; P < 0.05）。我们的结论是，无论是先天性的NOS 2缺陷或选择性抑制NOS 2保护小鼠从HPV的损害发生后6小时的HV（T）通气。
Hypoxic pulmonary vasoconstriction (HPV) preserves systemic arterial oxygenation during lung injury by diverting blood flow away from poorly ventilated lung regions. Ventilator-induced lung injury (VILI) is characterized by pulmonary inflammation, lung edema, and impaired HPV leading to systemic hypoxemia. Studying mice congenitally deficient in inducible nitric oxide synthase (NOS2) and wild-type mice treated with a selective NOS2 inhibitor, L-N(6)-(1-iminoethyl)lysine (L-NIL), we investigated the contribution of NOS2 to the impairment of HPV in anesthetized mice subjected to 6 h of either high tidal volume (HV(T)) or low tidal volume (LV(T)) ventilation. HPV was estimated by measuring the changes of left lung pulmonary vascular resistance (LPVR) in response to left mainstem bronchus occlusion (LMBO). LMBO increased the LPVR similarly in wild-type, NOS2(-/-), and wild-type mice treated with L-NIL 30 min before commencing 6 h of LV(T) ventilation (96% +/- 30%, 103% +/- 33%, and 80% +/- 16%, respectively, means +/- SD). HPV was impaired in wild-type mice subjected to 6 h of HV(T) ventilation (23% +/- 16%). In contrast, HPV was preserved after 6 h of HV(T) ventilation in NOS2(-/-) and wild-type mice treated with L-NIL either 30 min before or 6 h after commencing HV(T) ventilation (66% +/- 22%, 82% +/- 29%, and 85% +/- 16%, respectively). After 6 h of HV(T) ventilation and LMBO, systemic arterial oxygen tension was higher in NOS2(-/-) than in wild-type mice (192 +/- 11 vs. 171 +/- 17 mmHg; P < 0.05). We conclude that either congenital NOS2 deficiency or selective inhibition of NOS2 protects mice from the impairment of HPV occurring after 6 h of HV(T) ventilation.