High-altitude pulmonary hypertension is associated with a free radical-mediated reduction in pulmonary nitric oxide bioavailability
High-altitude pulmonary hypertension is associated with a free radical-mediated reduction in pulmonary nitric oxide bioavailability
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DOI：
10.1113/jphysiol.2010.194704
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发表时间：
2010-12-01
影响因子：
5.5
通讯作者：
Berger, Marc M.
中科院分区：
文献类型：
--
作者：
Bailey, Damian M.;Dehnert, Christoph;Berger, Marc M.
高海拔（HA）诱发的肺动脉高压可能是由于自由基介导的肺一氧化氮（NO）生物利用度降低所致。我们假设 HA 处肺动脉收缩压 (PASP) 的增加与自由基的净跨肺输出和相应的生物活性 NO 代谢物的损失有关。 26 名登山者在低海拔 (LA) 和主动攀登至 4559 m (HA) 后提供了中心静脉和桡动脉样本。 PASP 通过多普勒超声心动图测定，通过惰性气体再呼吸测定肺血流量，并通过菲克原理测定血管活性交换。急性高山病（AMS）和高原肺水肿（HAPE）通过临床问卷和胸部X光检查进行诊断。采用电子顺磁共振波谱、基于臭氧的化学发光和 ELISA 等离子检测抗坏血酸自由基（A 中心点-）、NO 代谢物和 3-硝基酪氨酸 (3-NT)。 14 名受试者被诊断患有 AMS，4 名 HAPE 易感受试者中的 3 名发展为 HAPE。上升降低了动-中心静脉浓度差 (a-cv(D))，导致抗坏血酸、α-生育酚和生物活性 NO 代谢物的净跨肺损失（与 LA 相比，P < 0.05）。这伴随着 a-cv(D) 的增加以及 A 中心点和脂质氢过氧化物的净输出（相对于海平面，SL，P < 0.05），与 PASP（r = 0.56-0.62，P < 0.05）和动脉 3-NT（r = 0.48-0.63，P < 0.05）的增加相关，这在 HAPE 中更为明显。这些发现表明，HA 处观察到的 PASP 和血管阻力增加与自由基介导的肺 NO 生物利用度降低有关。
High altitude (HA)-induced pulmonary hypertension may be due to a free radical-mediated reduction in pulmonary nitric oxide (NO) bioavailability. We hypothesised that the increase in pulmonary artery systolic pressure (PASP) at HA would be associated with a net transpulmonary output of free radicals and corresponding loss of bioactive NO metabolites. Twenty-six mountaineers provided central venous and radial arterial samples at low altitude (LA) and following active ascent to 4559 m (HA). PASP was determined by Doppler echocardiography, pulmonary blood flow by inert gas re-breathing, and vasoactive exchange via the Fick principle. Acute mountain sickness (AMS) and high-altitude pulmonary oedema (HAPE) were diagnosed using clinical questionnaires and chest radiography. Electron paramagnetic resonance spectroscopy, ozone-based chemiluminescence and ELISA were employed for plasma detection of the ascorbate free radical (A center dot-), NO metabolites and 3-nitrotyrosine (3-NT). Fourteen subjects were diagnosed with AMS and three of four HAPE-susceptible subjects developed HAPE. Ascent decreased the arterio-central venous concentration difference (a-cv(D)) resulting in a net transpulmonary loss of ascorbate, alpha-tocopherol and bioactive NO metabolites (P < 0.05 vs. LA). This was accompanied by an increased a-cv(D) and net output of A center dot- and lipid hydroperoxides (P < 0.05 vs. sea level, SL) that correlated against the rise in PASP (r = 0.56-0.62, P < 0.05) and arterial 3-NT (r = 0.48-0.63, P < 0.05) that was more pronounced in HAPE. These findings suggest that increased PASP and vascular resistance observed at HA are associated with a free radical-mediated reduction in pulmonary NO bioavailability.