Inorganic nitrate ingestion improves vascular compliance but does not alter flow-mediated dilatation in healthy volunteers.

Inorganic nitrate ingestion improves vascular compliance but does not alter flow-mediated dilatation in healthy volunteers.
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DOI:
10.1016/j.niox.2012.01.004
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发表时间:
2012-05-15
期刊:
Nitric oxide : biology and chemistry
影响因子:
--
通讯作者:
Ahluwalia A
Ahluwalia A
中科院分区:
其他
文献类型:
--
作者:
Bahra M;Kapil V;Pearl V;Ghosh S;Ahluwalia A

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补充无机硝酸盐不会改变健康志愿者的内皮功能。尽管如此,血压降低,动脉顺应性改善。►血管功能的改善可能有助于无机硝酸盐对血压的有益影响。无机硝酸盐的摄入通过肠-唾液循环中的生物转化提高血液和组织中的亚硝酸盐水平。亚硝酸盐在循环中转化为NO,正是这种现象被认为是无机硝酸盐对人体有益的基础。我们以前的研究表明,口服无机硝酸盐降低血压,抑制健康志愿者缺血再灌注损伤引起的短暂内皮功能障碍。然而,无机硝酸盐是否可能在没有致病刺激的情况下改善内皮功能本身,以及这是否可能有助于降低血压的作用,目前尚不清楚。我们在14名健康志愿者中进行了一项随机、双盲、交叉研究,以确定口服无机硝酸盐(8 mmol KNO 3)与安慰剂(8 mmol KCl)对内皮功能的影响,通过肱动脉的流量介导扩张(FMD)测量,在胶囊摄入前和3 h后。此外,测量血压(BP)和主动脉脉搏波速度(aPWV)。最后,在干预前和干预后3 h采集血液、唾液和尿液样本进行[亚硝酸盐]和[硝酸盐]的化学发光分析。无机硝酸盐补充对健康志愿者的内皮功能没有影响(KNO 3前为6.9 ± 1.1%,后为7.1 ± 1.1%)。尽管如此,血浆[亚硝酸盐]显著升高(KNO 3前0.4 ± 0.1 μM至KNO 3后0.7 ± 0.2 μM,p < 0.001)。此外,[亚硝酸盐]的这些变化与收缩压(KNO 3治疗前116.9 ± 3.8 mm Hg vs.治疗后112.1 ± 3.4 mm Hg,p < 0.05)和aPWV(KNO 3治疗前6.5 ± 0.1 m/s vs.治疗后6.2 ± 0.1 m/s,p < 0.01)降低相关。相比之下,KCl胶囊对测量的任何参数均无影响。这些研究结果表明,虽然无机硝酸盐摄入本身不会改变内皮功能,但它确实可以改善血流,并降低血压。这些变化可能是由于血管内NO的产生。
► Inorganic nitrate supplementation does not alter endothelial function in healthy volunteers. ► Despite this, there was a reduction in blood pressure and improvement in arterial compliance. ► Improvements in vascular function are likely to contribute to the beneficial effects of inorganic nitrate on blood pressure. Ingestion of inorganic nitrate elevates blood and tissue levels of nitrite via bioconversion in the entero-salivary circulation. Nitrite is converted to NO in the circulation, and it is this phenomenon that is thought to underlie the beneficial effects of inorganic nitrate in humans. Our previous studies have demonstrated that oral ingestion of inorganic nitrate decreases blood pressure and inhibits the transient endothelial dysfunction caused by ischaemia–reperfusion injury in healthy volunteers. However, whether inorganic nitrate might improve endothelial function per se in the absence of a pathogenic stimulus and whether this might contribute to the blood pressure lowering effects is yet unknown. We conducted a randomised, double-blind, crossover study in 14 healthy volunteers to determine the effects of oral inorganic nitrate (8 mmol KNO3) vs. placebo (8 mmol KCl) on endothelial function, measured by flow-mediated dilatation (FMD) of the brachial artery, prior to and 3 h following capsule ingestion. In addition, blood pressure (BP) was measured and aortic pulse wave velocity (aPWV) determined. Finally, blood, saliva and urine samples were collected for chemiluminescence analysis of [nitrite] and [nitrate] prior to and 3 h following interventions. Inorganic nitrate supplementation had no effect on endothelial function in healthy volunteers (6.9 ± 1.1% pre- to 7.1 ± 1.1% post-KNO3). Despite this, there was a significant elevation of plasma [nitrite] (0.4 ± 0.1 μM pre- to 0.7 ± 0.2 μM post-KNO3, p < 0.001). In addition these changes in [nitrite] were associated with a decrease in systolic BP (116.9 ± 3.8 mm Hg pre- vs. 112.1 ± 3.4 mm Hg post-KNO3, p < 0.05) and aPWV (6.5 ± 0.1 m/s pre- to 6.2 ± 0.1 post-KNO3, p < 0.01). In contrast KCl capsules had no effect on any of the parameters measured. These findings demonstrate that although inorganic nitrate ingestion does not alter endothelial function per se, it does appear to improve blood flow, in combination with a reduction in blood pressure. It is likely that these changes are due to the intra-vascular production of NO.
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