Nitric oxide signalling in kidney regulation and cardiometabolic health.
Nitric oxide signalling in kidney regulation and cardiometabolic health.
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DOI：
10.1038/s41581-021-00429-z
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发表时间：
2021-09
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影响因子：
--
通讯作者：
Carlström M
中科院分区：
文献类型：
--
作者：
Carlström M
心血管和代谢性疾病以及肾功能障碍在全球范围内的患病率正在增加。这三种疾病与相当大的发病率和死亡率以及巨大的经济负担有关。进一步了解其潜在的病理生理机制对于开发新的预防或治疗方法非常重要。在已提出的机制中，与氧化应激相关的一氧化氮(NO)生物活性受损被认为是重要的。NO是一种短暂的双原子信号分子，对肾脏、心脏和血管以及外周代谢活跃的器官产生多种影响。L精氨酸依赖的一氧化氮合酶途径被经典地认为是内源性一氧化氮形成的主要来源。然而，在包括肾脏、心血管和代谢性疾病在内的各种病理中，一氧化氮合酶系统的功能经常受到损害。另一种途径，硝酸盐-亚硝酸盐-NO途径，使内源或饮食来源的无机硝酸盐和亚硝酸盐能够通过一系列还原循环形成生物活性氮物种，包括NO，不依赖于NOS系统。通过这些氮物种的信号转导与cGMP依赖和独立的机制有关。在一氧化氮合酶缺乏和氧化应激期间恢复一氧化氮稳态的新方法在肾脏、心血管和代谢疾病方面具有潜在的治疗应用。一氧化氮(NO)在肾脏、心血管和代谢功能的调节中具有重要作用。本文讨论了NO的生理作用及其对肾功能的影响，以及它与心脏代谢并发症的关系，以及恢复NO稳态的新方法。一氧化氮和其他生物活性氮素在多种生理功能中起着关键作用，包括对肾脏、心血管系统和代谢系统的调节；在肾脏中，一氧化氮在自动调节和调节肾小管运输方面起着至关重要的作用。一氧化氮传统上来源于L精氨酸依赖的一氧化氮合酶，但也可以通过无机硝酸盐和亚硝酸盐的一系列还原即硝酸盐-亚硝酸盐-一氧化氮途径而形成。硝酸盐-亚硝酸盐-一氧化氮途径可以通过饮食促进，在一氧化氮合酶系统活性降低的条件下，如缺氧、缺血或低pH值，这一途径尤其重要。通过生物活性氮物种的信号传递与cGMP依赖和独立的机制都有关。一氧化氮生物活性降低与衰老、肾脏、心血管和代谢紊乱有关，这些疾病往往伴随着氧化应激。增加一氧化氮生物活性和减少氧化应激的新的药理和营养策略可能是预防和治疗肾脏疾病和相关的心脏代谢并发症的潜在疗法。
The prevalence of cardiovascular and metabolic disease coupled with kidney dysfunction is increasing worldwide. This triad of disorders is associated with considerable morbidity and mortality as well as a substantial economic burden. Further understanding of the underlying pathophysiological mechanisms is important to develop novel preventive or therapeutic approaches. Among the proposed mechanisms, compromised nitric oxide (NO) bioactivity associated with oxidative stress is considered to be important. NO is a short-lived diatomic signalling molecule that exerts numerous effects on the kidneys, heart and vasculature as well as on peripheral metabolically active organs. The enzymatic l-arginine-dependent NO synthase (NOS) pathway is classically viewed as the main source of endogenous NO formation. However, the function of the NOS system is often compromised in various pathologies including kidney, cardiovascular and metabolic diseases. An alternative pathway, the nitrate–nitrite–NO pathway, enables endogenous or dietary-derived inorganic nitrate and nitrite to be recycled via serial reduction to form bioactive nitrogen species, including NO, independent of the NOS system. Signalling via these nitrogen species is linked with cGMP-dependent and independent mechanisms. Novel approaches to restoring NO homeostasis during NOS deficiency and oxidative stress have potential therapeutic applications in kidney, cardiovascular and metabolic disorders. Nitric oxide (NO) has important roles in the regulation of kidney, cardiovascular and metabolic functions. This Review discusses the physiological roles of NO and its effects on kidney function, as well as its association with cardiometabolic complications and novel approaches to restoring NO homeostasis. Nitric oxide and other bioactive nitrogen species have pivotal roles in multiple physiological functions, including modulation of the kidney, cardiovascular and metabolic systems; in the kidney, nitric oxide has a crucial role in autoregulation and modulation of tubular transport. Nitric oxide is classically derived from l-arginine-dependent nitric oxide synthases, but can also be formed via serial reduction of inorganic nitrate and nitrite, that is, the nitrate–nitrite–nitric oxide pathway. The nitrate–nitrite–nitric oxide pathway can be boosted via the diet and is of particular importance in conditions where the activity of the nitric oxide synthase system is reduced, such as hypoxia, ischaemia or low pH. Signalling via bioactive nitrogen species is linked with both cGMP-dependent and independent mechanisms. Reduced nitric oxide bioactivity has been associated with ageing and kidney, cardiovascular and metabolic disorders, which are often coupled with oxidative stress. Novel pharmacological and nutritional strategies that increase nitric oxide bioactivity and reduce oxidative stress could be potential therapies for preventing and treating kidney disease and associated cardiometabolic complications.
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影响因子：
6.1
作者：
Bautista-Garcia, Pablo;Sanchez-Lozada, Laura Gabriela;Herrera-Acosta, Jaime
通讯作者：
Herrera-Acosta, Jaime
影响因子：
7.4
作者：
Bolden, Crystal;King, S. Bruce;Kim-Shapiro, Daniel B.
通讯作者：
Kim-Shapiro, Daniel B.
影响因子：
64.8
作者：
BREDT, DS;HWANG, PM;SNYDER, SH
通讯作者：
SNYDER, SH
DOI：
10.1161/atvbaha.110.209783
发表时间：
2010-10-01
影响因子：
8.7
作者：
Bucci, Mariarosaria;Papapetropoulos, Andreas;Cirino, Giuseppe
通讯作者：
Cirino, Giuseppe
DOI：
10.1152/ajprenal.1998.275.6.f870
发表时间：
1998-12-01
影响因子：
4.2
作者：
Broere, A;Van den MEiracker, AH;Schalekamp, MADH
通讯作者：
Schalekamp, MADH