Stahl Macy E, Grammer Emily E, Weltman Arthur, Burleigh Mia C, Derella Cassandra C, Abbate Antonio, Denicolai Martin, Allen Jason D
Department of Kinesiology, University of Virginia, Charlottesville, Virginia, United States.
Department of Medicine, University of Virginia, Charlottesville, Virginia, United States.
Am J Physiol Heart Circ Physiol. 2025 Oct 1;329(4):H952-H958. doi: 10.1152/ajpheart.00567.2025. Epub 2025 Sep 8.
Nitric oxide (NO) is essential for cardiovascular health and is purported as an ergogenic aid. Endothelial dysfunction and reduced endogenous NO production are hallmarks of heart failure (HF), which may contribute to impaired exercise capacity. Oral inorganic nitrate supplementation offers an exogenous route to increase bioavailable NO via reduction of nitrate by oral commensal bacteria. However, individuals with HF with reduced ejection fraction (HFrEF) display blunted increases in plasma nitrite and inconsistent improvements in exercise tolerance following supplementation. Thus, the purpose of this study was to examine whether bacterial oral nitrate-reducing capacity (ONRC) and markers of exercise capacity are impaired in patients with HFrEF compared with age-matched, healthy controls. Nine individuals with HFrEF [age: 74.89 ± 7.40 yr, peak oxygen consumption (V̇o): 15.17 ± 4.23 mL/kg/min; and 5 females and 4 males] and 9 healthy controls (CON) (age: 71.89 ± 4.23 yr, V̇o: 24.25 ± 2.86 mL/kg/min; and 4 females and 5 males) completed a V̇o test, ONRC assessment, and measures of salivary and plasma -oxides. ONRC and saliva nitrite were lower in HFrEF ( = 0.010 and = 0.018, respectively). ONRC for all participants was correlated with V̇o (ρ = 0.68; = 0.002) and oxygen consumption (V̇o) at ventilatory threshold (ρ = 0.81; < 0.001), though this relationship was not significant within groups. These data are first to suggest that ONRC may be impaired in HFrEF compared with age-matched, healthy adults. Future research in a larger sample is needed to determine if ONRC is associated with functional capacity in HFrEF. Although the link between cardiovascular disease and oral health has been established, the mechanisms underlying this relationship are not fully understood. These data are the first to suggest that the nitrate-reducing capacity of oral microbiota is lower in individuals with heart failure with reduced ejection fraction compared with healthy individuals, indicating that strategies to positively modulate the oral microbiome may improve the therapeutic potential of oral inorganic nitrate supplementation in heart failure.
一氧化氮（NO）对心血管健康至关重要，据称是一种促力剂。内皮功能障碍和内源性NO生成减少是心力衰竭（HF）的标志，这可能导致运动能力受损。口服无机硝酸盐补充剂提供了一条外源性途径，通过口腔共生细菌将硝酸盐还原，从而增加生物可利用的NO。然而，射血分数降低的心力衰竭（HFrEF）患者补充后血浆亚硝酸盐增加不明显，运动耐力改善也不一致。因此，本研究的目的是检验与年龄匹配的健康对照相比，HFrEF患者的口腔细菌硝酸盐还原能力（ONRC）和运动能力标志物是否受损。9名HFrEF患者[年龄：74.89±7.40岁，峰值耗氧量（V̇o₂）：15.17±4.23 mL/kg/min；5名女性和4名男性]和9名健康对照（CON）（年龄：71.89±4.23岁，V̇o₂：24.25±2.86 mL/kg/min；4名女性和5名男性）完成了V̇o₂测试、ONRC评估以及唾液和血浆氧化物测量。HFrEF患者的ONRC和唾液亚硝酸盐较低（分别为P = 0.010和P = 0.018）。所有参与者的ONRC与V̇o₂（ρ = 0.68；P = 0.002）以及通气阈值时的耗氧量（V̇o₂）（ρ = 0.81；P < 0.001）相关，尽管在组内这种关系不显著。这些数据首次表明，与年龄匹配的健康成年人相比，HFrEF患者的ONRC可能受损。需要在更大样本中进行进一步研究，以确定ONRC是否与HFrEF患者的功能能力相关。虽然心血管疾病与口腔健康之间的联系已经确立，但这种关系背后的机制尚未完全了解。这些数据首次表明，与健康个体相比，射血分数降低的心力衰竭患者口腔微生物群的硝酸盐还原能力较低，这表明积极调节口腔微生物群的策略可能会提高口服无机硝酸盐补充剂在心力衰竭中的治疗潜力。
