Role of endogenous nitric oxide (NO) on hypoxic pulmonary vasoconstriction and ventilation/perfusion mismatching

内源性一氧化氮（NO）对缺氧性肺血管收缩和通气/灌注不匹配的作用

• 批准号: 08670643
• 负责人: NAKANO Hitoshi
• 金额: $ 1.34万
• 依托单位: Asahikawa Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670643/
• 关键词: exhaled nitric oxide; NO metabolites; pulmonary circulation; isolated perfused lung; hypoxic pulmonary vasoconstriction; hemoglobin concentration; hypoxia; airway epithelia; 呼気中一酸化窒素

We measured pulmonary arterial pressure (Ppa), the concentration of exhaled NO (ex NO) and the accumulation of perfusate NO_2^-/NO_3^- (NO_x) in the isolated perfused rabbit lungs.1.The exNO from the buffer-perfused lungs decreased along with a increase in hematocrit with a hyperbolic fashion. Pulmonary blood flow did not affect the hematocrit-dependent decrease of exNO.These results suggest that exNO from the lung is cleared via the pulmonary blood for the physiological range of hematocrit. Therefore, the values of exNO which we measured is masked by circulating pulmonary blood and does not reflect the correct production of NO from the lung.2.A bolus injection of acetylcholine into the pulmonary artery evoked a transient increase of exNO with a decrease of Ppa while the NO_x remained unchanged. The step increase of flow caused corresponding elevation of the production rate of exNO,whereas NO_x did not change. L-NMMA caused a fall of exNO and NO_x with a rise of Ppa in the range of all flow rate. The pulmonary vascular conductance progressively increased along with flow rate in control state. However, L-NMMA blocked the flow-dependent increase of the conductance. These results suggest that flow-dependent increase of exNO is associated with pulmonary capillary recruitment.3.The exNO was gradually decreased along with a reduction of O_2 concentration and changing to normoxia exhibited a prompt increase of exNO.Decreasing O_2 tension reduced exNO curvilineally. This curvilinearl relationship between O_2 tension and exNO is similar to that between substrate concentration and enzyme-reaction velocity (Michaelis-Menten kinetics). We have demonstrated the exNO is synthesized enzymatically by using ambient oxygen as a substrate. This result suggests that epithelial NO synthesis itself may function as an 'oxygen sensor' in the airway and NO produced in the epithelium may play an important role in pulmonary pathophysiology.

我们测定了离体肺灌流后的肺动脉压(PPA)、呼出的NO浓度(Ex NO)和灌流液中NO_2~-/NO_3^-(NO_X)的积累量。1.缓冲灌流肺的呼出量随红细胞压积的升高而下降，呈双曲线关系。肺血流量不影响红细胞压积依赖性的exNO降低，提示exNO是通过肺血清除的，符合红细胞压积的生理范围。因此，我们测量的exNO值被循环的肺血液掩盖了，不能反映肺中正确的NO产生。2.向肺动脉注射乙酰胆碱可引起exNO的一过性增加，而PPA降低，而NO_x保持不变。流量的阶跃增加导致了exNO产率的相应提高，而NOx没有变化。在所有流量范围内，L-NMMA引起exNO和NO_x的下降，而PPA升高。对照状态下，肺血管电导随流速增加而递增。然而，L-NMMA阻断了电导随流量的增加。这些结果表明，exNO的流量依赖性增加与肺毛细血管的募集有关。3.随着O2浓度的降低，exNO逐渐减少，转为常压后exNO迅速增加。O_2张力与exNO之间的曲线关系类似于底物浓度与酶反应速度之间的曲线关系(米氏动力学)。我们已经证明了exNO是以环境氧为底物在酶作用下合成的。这一结果提示，上皮性NO合成本身可能是呼吸道的“氧感受器”，其产生的NO可能在肺的病理生理学中起重要作用。

项目成果

Nakano,Hitoshi.: "Hypoxia decreases exhaled NO in isolated buffer-perfused rabbitlungs." Am.J.Resp.Crit.Care Med.153(4). A186- (1996)

Nakano, Hitoshi.：“缺氧减少了隔离的缓冲液灌注兔肺中呼出的 NO。”

Ogasa, Toshiyuki.: "Flow-induced production of endothelial nitricoxide in buffer-perfused rabbit lungs." Am.J.Resp.Crit.Care Med.155(4). A824 (1997)

Ogasa，Toshiyuki：“在缓冲液灌注的兔肺中流动诱导内皮一氧化氮的产生。”

Nakano, Hitoshi: "Hypoxia decreases exhaled NO in isolated buffer-perfused rabbit lungs." Am.J.Resp.Crit.Care Med.153 (4). A186 (1996)

Nakano, Hitoshi：“缺氧会减少灌注缓冲液的兔肺中呼出的 NO 量。”

Iwamoto, Jun.: "Analysisu of single breath nitric oxide (SBVNO) in healthy subujects." FASEB J.11(3). A346 (1997)

Iwamoto, Jun.：“健康受试者单次呼吸一氧化氮 (SBVNO) 的分析。”

Ogasa, Toshiyuki: "Blood attenuates flow-dependent increase in exhaled NO in buffer-perfused rabbit lungs." Am.J.Resp.Crit.Care Med.153 (4). A186 (1996)

Ogasa, Toshiyuki：“血液减弱了缓冲液灌注的兔肺中呼出一氧化氮的流量依赖性增加。”