Hypoxemia and blunted hypoxic ventilatory responses in mice lacking heme oxygenase-2
Hypoxemia and blunted hypoxic ventilatory responses in mice lacking heme oxygenase-2
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DOI：
10.1016/j.bbrc.2004.05.195
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发表时间：
2004-07-23
影响因子：
3.1
通讯作者：
Shibahara, S
中科院分区：
文献类型：
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作者：
Adachi, T;Ishikawa, K;Shibahara, S
血红素加氧酶（HO）催化血红素的生理降解，由两种结构相关的同工酶HO-1和HO-2组成。在这里，我们发现HO-2缺陷（HO-2（-/-））小鼠表现出低氧血症和肺静脉心肌肥大与HO-1的表达增加。静脉心肌肥厚可能反映了对持续低氧血症的适应。HO-2（-/-）小鼠还显示对低氧（10%O-2）的减弱的呼吸反应，对高碳酸血症（10%CO2）的正常反应，表明氧感受损。重要的是，HO-2（-/-）小鼠表现出正常的呼吸模式，具有正常的动脉CO2张力，并保持完整的肺泡结构，从而排除了作为低氧血症原因的通气不足和分流。相反，通气-灌注不匹配可能是低氧血症的原因，这可能是由于肺动脉平滑肌细胞的肺化学感受性部分受损所致。因此，我们提出HO-2参与氧传感，并负责优化肺血氧合的通气-灌注匹配。(C)2004年爱思唯尔公司All rights reserved.
Heme oxygenase (HO) catalyzes physiological heme degradation and consists of two structurally related isozymes, HO-1 and HO-2. Here we show that HO-2-deficient (HO-2(-/-)) mice exhibit hypoxemia and hypertrophy of the pulmonary venous myocardium associated with increased expression of HO-1. The hypertrophied venous myocardium may reflect adaptation to persistent hypoxemia. HO-2(-/-) mice also show attenuated ventilatory responses to hypoxia (10% O-2) with normal responses to hypercapnia (10%, CO2), suggesting the impaired oxygen sensing, Importantly, HO-2(-/-) mice exhibit normal breathing patterns with normal arterial CO2 tension and retain the intact alveolar architecture, thereby excluding hypoventilation and shunting as causes of hypoxemia. Instead, ventilation-perfusion mismatch is a likely cause of hypoxemia, which may be due to partial impairment of the lung chemoreception probably at pulmonary artery smooth muscle cells. We therefore propose that HO-2 is involved in oxygen sensing and responsible for the ventilation-perfusion matching that optimizes oxygenation of pulmonary blood. (C) 2004 Elsevier Inc. All rights reserved.