Pharmaceutical Biology Laboratory, in Institute of Research for Food Safety & Health (IRC-FSH), Department of Health Sciences, University "Magna Graecia" of Catanzaro, 88100 Catanzaro, Italy.
Institute of Research for Food Safety & Health (IRC-FSH), Department of Health Sciences, University "Magna Graecia" of Catanzaro, 88100 Catanzaro, Italy.
Int J Mol Sci. 2022 Dec 7;23(24):15454. doi: 10.3390/ijms232415454.
Reduced bioavailability of the nitric oxide (NO) signaling molecule has been associated with the onset of cardiovascular disease. One of the better-known and effective therapies for cardiovascular disorders is the use of organic nitrates, such as glyceryl trinitrate (GTN), which increases the concentration of NO. Unfortunately, chronic use of this therapy can induce a phenomenon known as "nitrate tolerance", which is defined as the loss of hemodynamic effects and a reduction in therapeutic effects. As such, a higher dosage of GTN is required in order to achieve the same vasodilatory and antiplatelet effects. Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is a cardioprotective enzyme that catalyzes the bio-activation of GTN to NO. Nitrate tolerance is accompanied by an increase in oxidative stress, endothelial dysfunction, and sympathetic activation, as well as a loss of the catalytic activity of ALDH2 itself. On the basis of current knowledge, nitrate intake in the diet would guarantee a concentration of NO such as to avoid (or at least reduce) treatment with GTN and the consequent onset of nitrate tolerance in the course of cardiovascular diseases, so as not to make necessary the increase in GTN concentrations and the possible inhibition/alteration of ALDH2, which aggravates the problem of a positive feedback mechanism. Therefore, the purpose of this review is to summarize data relating to the introduction into the diet of some natural products that could assist pharmacological therapy in order to provide the NO necessary to reduce the intake of GTN and the phenomenon of nitrate tolerance and to ensure the correct catalytic activity of ALDH2.
一氧化氮（NO）信号分子的生物利用度降低与心血管疾病的发生有关。有机硝酸盐（如甘油三硝酸酯（GTN））是治疗心血管疾病的一种较好的和有效的方法，它可以增加 NO 的浓度。不幸的是，这种治疗的慢性使用会导致所谓的“硝酸盐耐受”现象，其定义为血流动力学效应的丧失和治疗效果的降低。因此，需要更高剂量的 GTN 才能达到相同的血管扩张和抗血小板作用。线粒体乙醛脱氢酶 2（ALDH2）是一种心脏保护酶，可催化 GTN 生物转化为 NO。硝酸盐耐受伴随着氧化应激、内皮功能障碍和交感神经激活的增加，以及 ALDH2 自身催化活性的丧失。根据目前的知识，饮食中的硝酸盐摄入可以保证一定浓度的 NO，从而避免（或至少减少）使用 GTN 治疗，并避免在心血管疾病过程中发生硝酸盐耐受，从而避免有必要增加 GTN 浓度以及可能的抑制/改变 ALDH2，这会加剧正反馈机制的问题。因此，本综述的目的是总结有关将一些天然产物引入饮食中的数据，这些天然产物可以辅助药物治疗，以提供必要的 NO，减少 GTN 的摄入和硝酸盐耐受现象，并确保 ALDH2 的正确催化活性。
