Acute intermittent hypercapnic hypoxia and sympathetic neurovascular transduction in men
Acute intermittent hypercapnic hypoxia and sympathetic neurovascular transduction in men
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DOI：
10.1113/jp278941
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发表时间：
2020-01-19
影响因子：
5.5
通讯作者：
Foster, Glen E.
中科院分区：
文献类型：
--
作者：
Stuckless, Troy J. R.;Vermeulen, Tyler D.;Foster, Glen E.
关键点间歇性缺氧导致肌肉交感神经活动和血压的长期增加，导致阻塞性睡眠呼吸暂停患者高血压风险增加。我们确定是否增强血管反应增加交感神经血管流出，称为交感神经血管转导（sNVT），伴随着血压的变化，急性间歇性高碳酸血症缺氧的男性。利用下体负压诱导一系列交感血管收缩剂放电，同时测量逐搏血压和前臂血管传导。IH降低血管切应力和陡峭的舒张压和交感神经放电频率之间的关系，表明更大的全身sNVT。我们的研究结果表明，阻塞性睡眠呼吸暂停的特征性急性间歇性高碳酸血症缺氧的反复循环可以通过增加sNVT来促进高血压。急性间歇性高碳酸血症性缺氧（IH）诱导健康人交感神经血管流出和血压的长期持续升高。目前尚不清楚IH是否改变交感神经血管转导（sNVT），测量交感神经血管流出与前臂血管传导（FVC;局部sNVT）或舒张压（全身sNVT）之间的关系。我们通过将健康男性暴露于40个连续的1分钟呼吸周期来验证IH增强sNVT的假设，每个呼吸周期包括40 s的高碳酸血症性缺氧（PETCO 2：高于基线+4 +/- 3 mmHg; PETO 2：48 +/- 3 mmHg）和20 s的常氧（n = 9），或40 min的空气呼吸对照（n = 7）。在干预前后，施加下体负压（LBNP;在-15、-30和-45 mmHg下3分钟），以在将潮气末气体夹持在基线水平时引起肌肉交感神经活动（MSNA，腓骨微神经造影）的反射增加。通气、动脉压[收缩压、舒张压、平均动脉压（MAP）]、肱动脉血流量（Q？(BA))、FVC（Q？(BA)/MAP）和MSNA爆发频率。IH后，但不是对照组，通气量[5 L min（-1）; 95%置信区间（CI）= 1-9]和MAP（5 mmHg; 95% CI = 1-9）增加，而FVC（-0.2 mL min（-1）mmHg（-1）; 95% CI = -0.0 to -0.4）和平均剪切速率（-21.9 s（-1）; 95% CI = -5.8 to -38.0;所有P < 0.05）降低。全身sNVT在IH后增加（0.25 mmHg爆发（-1）min（-1）; 95% CI = 0.01-0.49; P < 0.05），而局部前臂sNVT的变化在IH和假手术之间相似。血管壁剪切应力的降低，以及由此产生的一氧化氮的产生，可能导致全身sNVT升高，并为阻塞性睡眠呼吸暂停患者血压升高提供了潜在的神经血管机制。
Key pointsIntermittent hypoxia leads to long-lasting increases in muscle sympathetic nerve activity and blood pressure, contributing to increased risk for hypertension in obstructive sleep apnoea patients. We determined whether augmented vascular responses to increasing sympathetic vasomotor outflow, termed sympathetic neurovascular transduction (sNVT), accompanied changes in blood pressure following acute intermittent hypercapnic hypoxia in men. Lower body negative pressure was utilized to induce a range of sympathetic vasoconstrictor firing while measuring beat-by-beat blood pressure and forearm vascular conductance. IH reduced vascular shear stress and steepened the relationship between diastolic blood pressure and sympathetic discharge frequency, suggesting greater systemic sNVT. Our results indicate that recurring cycles of acute intermittent hypercapnic hypoxia characteristic of obstructive sleep apnoea could promote hypertension by increasing sNVT. Acute intermittent hypercapnic hypoxia (IH) induces long-lasting elevations in sympathetic vasomotor outflow and blood pressure in healthy humans. It is unknown whether IH alters sympathetic neurovascular transduction (sNVT), measured as the relationship between sympathetic vasomotor outflow and either forearm vascular conductance (FVC; regional sNVT) or diastolic blood pressure (systemic sNVT). We tested the hypothesis that IH augments sNVT by exposing healthy males to 40 consecutive 1 min breathing cycles, each comprising 40 s of hypercapnic hypoxia (PETCO2: +4 +/- 3 mmHg above baseline; PETO2: 48 +/- 3 mmHg) and 20 s of normoxia (n = 9), or a 40 min air-breathing control (n = 7). Before and after the intervention, lower body negative pressure (LBNP; 3 min at -15, -30 and -45 mmHg) was applied to elicit reflex increases in muscle sympathetic nerve activity (MSNA, fibular microneurography) when clamping end-tidal gases at baseline levels. Ventilation, arterial pressure [systolic blood pressure, diastolic blood pressure, mean arterial pressure (MAP)], brachial artery blood flow (Q?(BA)), FVC (Q?(BA)/MAP) and MSNA burst frequency were measured continuously. Following IH, but not control, ventilation [5 L min(-1); 95% confidence interval (CI) = 1-9] and MAP (5 mmHg; 95% CI = 1-9) were increased, whereas FVC (-0.2 mL min(-1) mmHg(-1); 95% CI = -0.0 to -0.4) and mean shear rate (-21.9 s(-1); 95% CI = -5.8 to -38.0; all P < 0.05) were reduced. Systemic sNVT was increased following IH (0.25 mmHg burst(-1) min(-1); 95% CI = 0.01-0.49; P < 0.05), whereas changes in regional forearm sNVT were similar between IH and sham. Reductions in vessel wall shear stress and, consequently, nitric oxide production may contribute to heightened systemic sNVT and provide a potential neurovascular mechanism for elevated blood pressure in obstructive sleep apnoea.