Institute of Biology, Pomeranian University in Słupsk, Arciszewski Str. 22b, 76-200 Słupsk, Poland,
Department of Ecology, Geography and Nature Management, T.H. Shevchenko National University "Chernihiv Colehium", 53 Hetmana Polubotka Str., Chernihiv, 14013, Ukraine.
Cell Physiol Biochem. 2024 Jun 10;58(3):226-249. doi: 10.33594/000000705.
BACKGROUND/AIMS: Important benefits of intermittent hypoxic training (IHT) have emerged as an effective tool for enhancing adaptive potential in different pathological states, among which acute hypoxia dominates. Therefore, the aim of our study was to evaluate the mechanisms related to the effects of the nitric oxide system (nitrites, nitrates, carbamide, and total polyamine content) on ADP-stimulated oxygen consumption and oxidative phosphorylation in heart and liver mitochondria and biomarkers of oxidative stress in the blood, heart, and liver of rats exposed to the IHT method and acute hypoxia and treated with the amino acid L-arginine (600 mg/kg, 30 min) or the NO synthase inhibitor L-NNA (35 mg/kg, 30 min) prior to each IHT session.
We analysed the modulation of the system of oxygen-dependent processes (mitochondrial respiration with the oxygraphic method, microsomal oxidation, and lipoperoxidation processes using biochemical methods) in tissues during IHT in the formation of short-term and long-term effects (30, 60, and 180 days after the last IHT session) with simultaneous administration of L-arginine. In particular, we investigated how mitochondrial functions are modulated during intermittent hypoxia with the use of oxidation substrates (succinate or α-ketoglutarate) in bioenergetic mechanisms of cellular stability and adaptation.
The IHT method is associated with a significant increase in the production of endogenous nitric oxide measured by the levels of its stable metabolite, nitrite anion, in both plasma (almost 7-fold) and erythrocytes (more than 7-fold) of rats. The intensification of nitric oxide-dependent pathways of metabolic transformations in the energy supply processes in the heart and liver, accompanied by oscillatory mechanisms of adaptation in the interval mode, causes a probable decrease in the production of urea and polyamines in plasma and liver, but not in erythrocytes. The administration of L-arginine prior to the IHT sessions increased the level of the nitrite-reducing component of the nitric oxide cycle, which persisted for up to 180 days of the experiment.
Thus, the efficacy of IHT and its nitrite-dependent component shown in this study is associated with the formation of long-term adaptive responses by preventing the intensification of lipoperoxidation processes in tissues due to pronounced changes in the main enzymes of antioxidant defence and stabilisation of erythrocyte membranes, which has a pronounced protective effect on the system of regulation of oxygen-dependent processes as a whole.
背景/目的：间歇性低氧训练（IHT）作为一种增强不同病理状态下适应能力的有效工具，具有重要的益处，其中急性低氧占主导地位。因此，我们的研究目的是评估与一氧化氮系统（亚硝酸盐、硝酸盐、尿素和总多胺含量）相关的机制，这些机制与 ADP 刺激的耗氧量和心脏和肝脏线粒体的氧化磷酸化以及暴露于 IHT 方法和急性低氧的大鼠血液、心脏和肝脏中的氧化应激生物标志物有关，并在每次 IHT 前用氨基酸 L-精氨酸（600mg/kg，30 分钟）或一氧化氮合酶抑制剂 L-NNA（35mg/kg，30 分钟）进行处理。
我们使用生化方法分析了 IHT 期间系统氧依赖过程（使用测氧仪进行线粒体呼吸、微粒体氧化和脂质过氧化过程）的调节，以及短期和长期效应（最后一次 IHT 后 30、60 和 180 天），同时给予 L-精氨酸。特别是，我们研究了在间歇性低氧的情况下，如何通过使用氧化底物（琥珀酸或α-酮戊二酸）来调节线粒体功能，从而在细胞稳定性和适应的生物能量机制中发挥作用。
IHT 方法与内源性一氧化氮的产生显著增加有关，这可以通过其稳定代谢物亚硝酸盐阴离子在大鼠血浆（几乎增加 7 倍）和红细胞（增加 7 倍以上）中的水平来衡量。在心脏和肝脏的能量供应过程中，依赖于一氧化氮的代谢转化途径的加强，伴随着间隔模式下适应的振荡机制，可能导致血浆和肝脏中尿素和多胺的产生减少，但红细胞中没有。在 IHT 前给予 L-精氨酸增加了一氧化氮循环的亚硝酸盐还原成分的水平，这种情况持续到实验的 180 天。
因此，本研究中 IHT 及其亚硝酸盐依赖成分的有效性与形成长期适应反应有关，因为组织中脂质过氧化过程的加剧由于抗氧化防御的主要酶的显著变化和红细胞膜的稳定而得到预防，这对整个氧依赖过程的调节系统具有明显的保护作用。
