King's College London British Heart Foundation Centre, Cardiovascular Division, Department of Clinical Pharmacology, London, UK.
Nitric Oxide. 2012 May 15;26(4):229-40. doi: 10.1016/j.niox.2012.03.008. Epub 2012 Apr 2.
Although both organic and inorganic nitrates/nitrites mediate their principal effects via nitric oxide, there are many important differences. Inorganic nitrate and nitrite have simple ionic structures and are produced endogenously and are present in the diet, whereas their organic counterparts are far more complex, and, with the exception of ethyl nitrite, are all medicinally synthesised products. These chemical differences underlie the differences in pharmacokinetic properties allowing for different modalities of administration, particularly of organic nitrates, due to the differences in their bioavailability and metabolic profiles. Whilst the enterosalivary circulation is a key pathway for orally ingested inorganic nitrate, preventing an abrupt effect or toxic levels of nitrite and prolonging the effects, this is not used by organic nitrates. The pharmacodynamic differences are even greater; while organic nitrates have potent acute effects causing vasodilation, inorganic nitrite's effects are more subtle and dependent on certain conditions. However, in chronic use, organic nitrates are considerably limited by the development of tolerance and endothelial dysfunction, whereas inorganic nitrate/nitrite may compensate for diminished endothelial function, and tolerance has not been reported. Also, while inorganic nitrate/nitrite has important cytoprotective effects against ischaemia-reperfusion injury, continuous use of organic nitrates may increase injury. While there are concerns that inorganic nitrate/nitrite may induce carcinogenesis, direct evidence of this in humans is lacking. While organic nitrates may continue to dominate the therapeutic arena, this may well change with the increasing recognition of their limitations, and ongoing discovery of beneficial effects and specific advantages of inorganic nitrate/nitrite.
尽管有机硝酸盐/亚硝酸盐和无机硝酸盐/亚硝酸盐都通过一氧化氮来发挥主要作用，但它们之间存在许多重要差异。无机硝酸盐和亚硝酸盐具有简单的离子结构，内源性产生并存在于饮食中，而它们的有机对应物则要复杂得多，除了亚硝酸乙酯外，它们都是药用合成产物。这些化学差异是药代动力学特性差异的基础，使得不同的给药方式成为可能，特别是有机硝酸盐，这是由于它们的生物利用度和代谢谱的差异。虽然肠-唾液循环是口服摄入无机硝酸盐的关键途径，可以防止亚硝酸盐的突然作用或毒性水平，并延长其作用，但有机硝酸盐并不利用这种途径。药效学差异甚至更大；虽然有机硝酸盐具有强大的急性血管扩张作用，但无机亚硝酸盐的作用则更为微妙，取决于某些条件。然而，在慢性使用中，有机硝酸盐因产生耐受性和内皮功能障碍而受到极大限制，而无机硝酸盐/亚硝酸盐可能会补偿内皮功能的下降，且目前尚未报告其产生耐受性。此外，虽然无机硝酸盐/亚硝酸盐对缺血再灌注损伤具有重要的细胞保护作用，但连续使用有机硝酸盐可能会增加损伤。虽然人们担心无机硝酸盐/亚硝酸盐可能会诱发致癌作用，但目前还缺乏人类直接证据。虽然有机硝酸盐可能继续主导治疗领域，但随着对其局限性的认识不断提高，以及对无机硝酸盐/亚硝酸盐有益作用和特定优势的不断发现，这种情况可能会发生变化。
