Nitric oxide (NO) from endothelial NO synthase importantly contributes to vascular homeostasis. Reduced NO production or increased scavenging during disease conditions with oxidative stress contribute to endothelial dysfunction and NO deficiency. In addition to the classical enzymatic NO synthases (NOS) system, NO can also be generated via the nitrate-nitrite-NO pathway. Dietary and pharmacological approaches aimed at increasing NO bioactivity, especially in the cardiovascular system, have been the focus of much research since the discovery of this small gaseous signaling molecule. Despite wide appreciation of the biological role of NOS/NO signaling, questions still remain about the chemical nature of NOS-derived bioactivity. Recent studies show that NO-like bioactivity can be efficiently transduced by mobile NO-ferroheme species, which can transfer between proteins, partition into a hydrophobic phase, and directly activate the soluble guanylyl cyclase-cGMP-protein kinase G pathway without intermediacy of free NO. Moreover, interaction between red blood cells and the endothelium in the regulation of vascular NO homeostasis have gained much attention, especially in conditions with cardiometabolic disease. In this review we discuss both classical and nonclassical pathways for NO generation in the cardiovascular system and how these can be modulated for therapeutic purposes.

中文翻译：

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心血管系统中的一氧化氮信号传导和调节：最新进展


来自内皮 NO 合酶的一氧化氮 （NO） 对血管稳态有重要贡献。在氧化应激的疾病条件下，NO 产生减少或清除增加会导致内皮功能障碍和 NO 缺乏。除了经典的酶促 NO 合酶 （NOS） 系统外，还可以通过硝酸盐-亚硝酸盐-NO 途径产生 NO。自从发现这种小的气态信号分子以来，旨在增加 NO 生物活性的饮食和药理学方法，尤其是在心血管系统中，一直是许多研究的重点。尽管 NOS/NO 信号转导的生物学作用得到了广泛认可，但关于 NOS 衍生生物活性的化学性质仍然存在疑问。最近的研究表明，NO 样生物活性可以被移动的 NO-铁血红素物种高效转导，它可以在蛋白质之间转移，分配成疏水相，直接激活可溶性鸟苷酸环化酶-cGMP-蛋白激酶 G 通路，而无需游离 NO 的中介。此外，红细胞和内皮细胞在调节血管 NO 稳态中的相互作用已受到广泛关注，尤其是在心脏代谢疾病的情况下。在这篇综述中，我们讨论了心血管系统中 NO 产生的经典和非经典途径，以及如何为治疗目的调节这些途径。