Acute inorganic nitrate supplementation and the hypoxic ventilatory response in patients with obstructive sleep apnea
Acute inorganic nitrate supplementation and the hypoxic ventilatory response in patients with obstructive sleep apnea
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DOI：
10.1152/japplphysiol.00696.2020
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发表时间：
2021-01-01
影响因子：
3.3
通讯作者：
Casey, Darren P.
中科院分区：
文献类型：
--
作者：
Bock, Joshua M.;Hanson, Brady E.;Casey, Darren P.
阻塞性睡眠呼吸暂停（OSA）患者心血管疾病风险增加，主要归因于高血压。增强的外周化学反射敏感性（即，对缺氧的过度反应）促进这些患者的高血压。一氧化氮钝化外周化学反射，OSA患者一氧化氮的生物利用度降低。因此，我们采用随机、双盲、安慰剂对照的交叉设计，研究了急性无机硝酸盐补充（甜菜根汁）（一种外源性一氧化氮来源）对OSA患者血压和缺氧心肺反应的剂量依赖性影响。14名OSA患者（53 ± 10岁，29.2 ± 5.8 kg/m2，呼吸暂停低通气指数=17.8 ± 8.1，43%F）完成了3次访视。在急性无机硝酸盐补充前和补充后2小时测量静息肱动脉血压和对吸气性缺氧的心肺反应[类似于0.10 mmol（安慰剂），4.03 mmol（低剂量）和8.06 mmol（高剂量）]。安慰剂既不增加血浆[硝酸盐]（30 +/- 52至52 +/- 23 μ M，P = 0.26）也不[亚硝酸盐]（266 +/- 153至277 +/- 164 nM，P = 0.21）;然而，这两个数字在低（29 +/- 17至175 +/- 42 μ M，220 +/- 137至514 +/- 352 nM）和高剂量（分别为26 +/- 11至292 +/- 90 μ M，248 +/- 155至738 +/-427 nM，所有P < 0.01）。服用安慰剂后，收缩压升高（120 +/- 9至128 +/- 10 mmHg，P < 0.05），而低剂量（121 +/- 11至123 +/- 8 mmHg，P = 0.19）或高剂量（124 +/- 13至124 +/- 9 mmHg，P = 0.96）后未观察到变化。安慰剂组对缺氧的最大缓解反应增加（3.1 +/- 1.2至4.4 +/- 2.6 L/min，P < 0.01），但不是低剂量组（4.4 +/- 2.4至5.4 +/- 3.4 L/min，P = 0.11）或高剂量组（4.3 +/- 2.3至4.8 +/- 2.7 L/min，P = 0.42）。无机硝酸盐没有改变心率反应缺氧（饮料的时间P = 0.64）。急性无机硝酸盐补充剂似乎可以通过抑制阻塞性睡眠呼吸暂停综合征患者的外周化学反射敏感性来抑制清晨收缩压的上升。新&值得注意本研究是第一个研究无机硝酸盐补充剂对静息血压和心肺反应的急性影响缺氧（例如，外周化学反射敏感性）。我们的数据表明，无机硝酸盐补充剂减弱了清晨收缩压的上升，这可能归因于外周化学反射敏感性减弱。这些数据表明，无机硝酸盐补充剂可以降低OSA患者患心血管疾病的风险。
Patients with obstructive sleep apnea (OSA) have increased cardiovascular disease risk largely attributable to hypertension. Heightened peripheral chemoreflex sensitivity (i.e., exaggerated responsiveness to hypoxia) facilitates hypertension in these patients. Nitric oxide blunts the peripheral chemoreflex, and patients with OSA have reduced nitric oxide bioavailability. We therefore investigated the dose-dependent effects of acute inorganic nitrate supplementation (beetroot juice), an exogenous nitric oxide source, on blood pressure and cardiopulmonary responses to hypoxia in patients with OSA using a randomized, double-blind, placebo-controlled crossover design. Fourteen patients with OSA (53 +/- 10 yr, 29.2 +/- 5.8 kg/m(2), apnea-hypopnea index=17.8 +/- 8.1, 43%F) completed three visits. Resting brachial blood pressure and cardiopulmonary responses to inspiratory hypoxia were measured before, and 2 h after, acute inorganic nitrate supplementation [similar to 0.10 mmol (placebo), 4.03 mmol (low dose), and 8.06 mmol (high dose)]. Placebo increased neither plasma [nitrate] (30 +/- 52 to 52 +/- 23 mu M, P = 0.26) nor [nitrite] (266 +/- 153 to 277 +/- 164 nM, P = 0.21); however, both increased following low (29 +/- 17 to 175 +/- 42 mu M, 220 +/- 137 to 514 +/- 352 nM) and high doses (26 +/- 11 to 292 +/- 90 mu M, 248 +/- 155 to 738 +/- 427nM, respectively, P < 0.01 for all). Following placebo, systolic blood pressure increased (120 +/- 9 to 128 +/- 10 mmHg, P < 0.05), whereas no changes were observed following low (121 +/- 11 to 123 +/- 8 mmHg, P = 0.19) or high doses (124 +/- 13 to 124 +/- 9 mmHg, P = 0.96). The peak ventilatory response to hypoxia increased following placebo (3.1 +/- 1.2 to 4.4 +/- 2.6 L/min, P < 0.01) but not low (4.4 +/- 2.4 to 5.4 +/- 3.4 L/min, P = 0.11) or high doses (4.3 +/- 2.3 to 4.8 +/- 2.7 L/min, P = 0.42). Inorganic nitrate did not change the heart rate responses to hypoxia (beverage-by-time P = 0.64). Acute inorganic nitrate supplementation appears to blunt an early-morning rise in systolic blood pressure potentially through suppression of peripheral chemoreflex sensitivity in patients with OSA.NEW & NOTEWORTHY The present study is the first to examine the acute effects of inorganic nitrate supplementation on resting blood pressure and cardiopulmonary responses to hypoxia (e.g., peripheral chemoreflex sensitivity) in patients with obstructive sleep apnea (OSA). Our data indicate inorganic nitrate supplementation attenuates an early-morning rise in systolic blood pressure potentially attributable to blunted peripheral chemoreflex sensitivity. These data show proof-of-concept that inorganic nitrate supplementation could reduce the risk of cardiovascular disease in patients with OSA.