The Nitrate-Nitrite-NO Pathway and Its Implications for Heart Failure and Preserved Ejection Fraction.
The Nitrate-Nitrite-NO Pathway and Its Implications for Heart Failure and Preserved Ejection Fraction.
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DOI：
10.1007/s11897-016-0277-9
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发表时间：
2016-02-01
影响因子：
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通讯作者：
Zamani, Payman
中科院分区：
文献类型：
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作者：
Chirinos, Julio A;Zamani, Payman
心力衰竭和射血分数保留（HFpEF）患者运动不耐受的发病机制可能是多因素的。除了心脏异常（舒张功能障碍、收缩储备异常、变时性功能不全）外，还可能涉及多种外周异常。这些包括异常脉动血流动力学，异常动脉血管舒张反应的运动，和异常外周O2输送，提取和利用。硝酸盐-亚硝酸盐-NO途径正在成为改变关键生理异常的潜在靶点，包括来自动脉波反射的收缩晚期左心室（LV）负荷（对LV具有有害的短期和长期后果）、动脉血管舒张储备、肌肉O2输送和骨骼肌线粒体功能。在最近完成的一项随机试验中，单剂量外源性无机硝酸盐的给药已被证明可产生各种有益的动脉血流动力学效应，最终导致HFpEF患者有氧能力增强。这些效果有可能立即改善运动耐量和长期的“疾病改善”效果。在这篇综述中，我们概述了HFpEF运动不耐受的关键机制因素，以及靶向硝酸盐-亚硝酸盐-NO途径的药物的潜在治疗作用。
The pathogenesis of exercise intolerance in patients with heart failure and preserved ejection fraction (HFpEF) is likely multifactorial. In addition to cardiac abnormalities (diastolic dysfunction, abnormal contractile reserve, chronotropic incompetence), several peripheral abnormalities are likely to be involved. These include abnormal pulsatile hemodynamics, abnormal arterial vasodilatory responses to exercise, and abnormal peripheral O2 delivery, extraction, and utilization. The nitrate-nitrite-NO pathway is emerging as a potential target to modify key physiologic abnormalities, including late systolic left ventricular (LV) load from arterial wave reflections (which has deleterious short- and long-term consequences for the LV), arterial vasodilatory reserve, muscle O2 delivery, and skeletal muscle mitochondrial function. In a recently completed randomized trial, the administration of a single dose of exogenous inorganic nitrate has been shown to exert various salutary arterial hemodynamic effects, ultimately leading to enhanced aerobic capacity in patients with HFpEF. These effects have the potential for both immediate improvements in exercise tolerance and for long-term "disease-modifying" effects. In this review, we provide an overview of key mechanistic contributors to exercise intolerance in HFpEF, and of the potential therapeutic role of drugs that target the nitrate-nitrite-NO pathway.