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补充无机硝酸盐可减弱外周化学感受反射敏感性,但不能改善老年人的心迷走反射敏感性。

Inorganic nitrate supplementation attenuates peripheral chemoreflex sensitivity but does not improve cardiovagal baroreflex sensitivity in older adults.

机构信息

Department of Physical Therapy and Rehabilitation Science, Carver College of Medicine, University of Iowa , Iowa City, Iowa.

Department of Anesthesia, Carver College of Medicine, University of Iowa , Iowa City, Iowa.

出版信息

Am J Physiol Heart Circ Physiol. 2018 Jan 1;314(1):H45-H51. doi: 10.1152/ajpheart.00389.2017. Epub 2017 Sep 29.

Abstract

Aging is associated with increased peripheral chemoreceptor activity, reduced nitric oxide (NO) bioavailability, and attenuation of cardiovagal baroreflex sensitivity (BRS), collectively increasing the risk of cardiovascular disease. Evidence suggests that NO may attenuate peripheral chemoreflex sensitivity and increase BRS. Exogenous inorganic nitrate ([Formula: see text]) increases NO bioavailability via the [Formula: see text]-[Formula: see text]-NO pathway. Our hypothesis was that inorganic [Formula: see text] supplementation would attenuate peripheral chemoreflex sensitivity and enhance spontaneous cardiovagal BRS in older adults. We used a randomized, placebo-controlled crossover design in which 13 older (67 ± 3 yr old) adults ingested beetroot powder containing (BR) or devoid of (BR) [Formula: see text] and [Formula: see text] daily over 4 wk. Spontaneous cardiovagal BRS was assessed over 15 min of rest and was quantified using the sequence method. Chemoreflex sensitivity was assessed via ~5 min of hypoxia (10% fraction of inspired O) and reported as the slope of the relationship between O saturation (%[Formula: see text]) and minute ventilation (in l/min) or heart rate (in beats/min). Ventilatory responsiveness to hypoxia was reduced after BR (from -0.14 ± 0.04 to -0.05 ± 0.02 l·min·%[Formula: see text], P = 0.01) versus BR (from -0.10 ± 0.05 to -0.11 ± 0.05 l·min·%[Formula: see text], P = 0.80), with no differences in heart rate responsiveness (BR: from -0.47 ± 0.06 to -0.33 ± 0.04 beats·min·%[Formula: see text], BR: from -0.48 ± 0.07 to -0.42 ± 0.06 beats·min·%[Formula: see text]) between conditions (interaction effect, P = 0.41). Spontaneous cardiovagal BRS was unchanged after BR and BR (interaction effects, P = 0.69, 0.94, and 0.39 for all, up, and down sequences, respectively), despite a reduction in resting systolic and mean arterial blood pressure in the experimental (BR) group ( P < 0.01 for both). These findings illustrate that inorganic [Formula: see text] supplementation attenuates peripheral chemoreflex sensitivity without concomitant change in spontaneous cardiovagal BRS in older adults. NEW & NOTEWORTHY Exogenous inorganic nitrate supplementation attenuates ventilatory, but not heart rate, responsiveness to abbreviated hypoxic exposure in older adults. Additionally, inorganic nitrate reduces systolic and mean arterial blood pressure without affecting spontaneous cardiovagal baroreflex sensitivity. These findings suggest that inorganic nitrate may attenuate sympathetically oriented pathologies associated with aging.

摘要

衰老是外周化学感受器活性增加、一氧化氮(NO)生物利用度降低以及心迷走反射压力敏感性(BRS)减弱的结果,这些因素共同增加了心血管疾病的风险。有证据表明,NO 可能会减弱外周化学感受器的敏感性并增加 BRS。外源性无机硝酸盐([化学式:见文本])通过[化学式:见文本]-[化学式:见文本]-NO 途径增加 NO 生物利用度。我们的假设是,无机[化学式:见文本]补充会减弱老年人的外周化学感受器敏感性并增强自主心迷走 BRS。我们使用了一项随机、安慰剂对照的交叉设计,其中 13 名老年人(67 ± 3 岁)在 4 周内每天摄入含有(BR)或不含(BR)[化学式:见文本]和[化学式:见文本]的甜菜根粉。自主心迷走 BRS 在休息 15 分钟内进行评估,并使用序列法进行量化。通过约 5 分钟的缺氧(吸入 O2 的 10%分数)评估化学感受器敏感性,并报告氧饱和度(%[化学式:见文本])与分钟通气量(l/min)或心率(beats/min)之间关系的斜率。BR 后,对缺氧的通气反应性降低(从 -0.14 ± 0.04 降至 -0.05 ± 0.02 l·min·%[化学式:见文本],P = 0.01),而 BR 后没有差异(从 -0.10 ± 0.05 降至 -0.11 ± 0.05 l·min·%[化学式:见文本],P = 0.80),两种情况下心率反应性均无差异(BR:从 -0.47 ± 0.06 降至 -0.33 ± 0.04 beats·min·%[化学式:见文本],BR:从 -0.48 ± 0.07 降至 -0.42 ± 0.06 beats·min·%[化学式:见文本])(交互作用,P = 0.41)。BR 和 BR 后自主心迷走 BRS 均无变化(交互作用,P = 0.69、0.94 和 0.39,分别用于所有、上升和下降序列),尽管实验(BR)组的静息收缩压和平均动脉血压降低(均 P < 0.01)。这些发现表明,外源性无机[化学式:见文本]补充可减弱老年人的外周化学感受器敏感性,而不伴自主心迷走 BRS 的变化。新与值得注意的是,外源性无机硝酸盐补充可减弱老年人对短暂缺氧暴露的通气反应性,但不影响心率反应性。此外,无机硝酸盐降低收缩压和平均动脉血压,而不影响自主心迷走反射压力敏感性。这些发现表明,无机硝酸盐可能会减弱与衰老相关的交感神经定向病理。

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