Department of Physical Therapy & Rehabilitation Science, University of Iowa, Iowa City, Iowa.
Department of Anesthesia, University of Iowa, Iowa City, Iowa.
J Appl Physiol (1985). 2021 Jan 1;130(1):87-95. doi: 10.1152/japplphysiol.00696.2020. Epub 2020 Nov 19.
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, 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 [∼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 μM, = 0.26) nor [nitrite] (266 ± 153 to 277 ± 164 nM, = 0.21); however, both increased following low (29 ± 17 to 175 ± 42 μM, 220 ± 137 to 514 ± 352 nM) and high doses (26 ± 11 to 292 ± 90 μM, 248 ± 155 to 738 ± 427 nM, respectively, < 0.01 for all). Following placebo, systolic blood pressure increased (120 ± 9 to 128 ± 10 mmHg, < 0.05), whereas no changes were observed following low (121 ± 11 to 123 ± 8 mmHg, = 0.19) or high doses (124 ± 13 to 124 ± 9 mmHg, = 0.96). The peak ventilatory response to hypoxia increased following placebo (3.1 ± 1.2 to 4.4 ± 2.6 L/min, < 0.01) but not low (4.4 ± 2.4 to 5.4 ± 3.4 L/min, = 0.11) or high doses (4.3 ± 2.3 to 4.8 ± 2.7 L/min, = 0.42). Inorganic nitrate did not change the heart rate responses to hypoxia (beverage-by-time = 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. 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.
患有阻塞性睡眠呼吸暂停（OSA）的患者心血管疾病风险增加，这在很大程度上归因于高血压。外周化学感受器敏感性升高（即对缺氧的反应过度）促进了这些患者的高血压。一氧化氮使外周化学感受器迟钝，而 OSA 患者的一氧化氮生物利用度降低。因此，我们使用随机、双盲、安慰剂对照交叉设计，研究了急性无机硝酸盐补充（甜菜汁），一种外源性一氧化氮源，对 OSA 患者缺氧时血压和心肺反应的剂量依赖性影响。14 名 OSA 患者（53±10 岁，29.2±5.8kg/m，呼吸暂停-低通气指数=17.8±8.1，43%F）完成了三次访问。在急性无机硝酸盐补充[约 0.10mmol（安慰剂）、4.03mmol（低剂量）和 8.06mmol（高剂量）]前后测量了静息肱动脉血压和心肺对吸气性缺氧的反应。安慰剂既没有增加血浆[硝酸盐]（30±52 至 52±23μM， = 0.26）也没有增加[亚硝酸盐]（266±153 至 277±164nM， = 0.21）；然而，低剂量（29±17 至 175±42μM，220±137 至 514±352nM）和高剂量（26±11 至 292±90μM，248±155 至 738±427nM）均增加了，所有结果均 < 0.01）。安慰剂后收缩压升高（120±9 至 128±10mmHg， < 0.05），而低剂量（121±11 至 123±8mmHg， = 0.19）或高剂量（124±13 至 124±9mmHg， = 0.96）则无变化。安慰剂后，缺氧时的最大通气反应增加（3.1±1.2 至 4.4±2.6L/min， < 0.01），但低剂量（4.4±2.4 至 5.4±3.4L/min， = 0.11）或高剂量（4.3±2.3 至 4.8±2.7L/min， = 0.42）则没有增加。硝酸盐对缺氧时的心率反应没有变化（饮料-时间 = 0.64）。急性无机硝酸盐补充似乎通过抑制 OSA 患者的外周化学感受器敏感性来抑制清晨收缩压的升高。本研究首次在 OSA 患者中检查了无机硝酸盐补充对静息血压和心肺对缺氧反应（例如外周化学感受器敏感性）的急性影响。我们的数据表明，无机硝酸盐补充可以减轻清晨收缩压的升高，这可能归因于外周化学感受器敏感性降低。这些数据表明，无机硝酸盐补充可以降低 OSA 患者患心血管疾病的风险。
