Cardiovascular disease remains the leading cause of death worldwide despite major advances in technology and treatment, with coronary heart disease (CHD) being a key contributor. Following an acute myocardial infarction (AMI), it is imperative that blood flow is rapidly restored to the ischaemic myocardium. However, this restoration is associated with an increased risk of additional complications and further cardiomyocyte death, termed myocardial ischaemia reperfusion injury (IRI). Endogenously produced nitric oxide (NO) plays an important role in protecting the myocardium from IRI. It is well established that NO mediates many of its downstream functions through the ‘canonical’ NO-sGC-cGMP pathway, which is vital for cardiovascular homeostasis; however, this pathway can become impaired in the face of inadequate delivery of necessary substrates, in particular L-arginine, oxygen and reducing equivalents. Recently, it has been shown that during conditions of ischaemia an alternative pathway for NO generation exists, which has become known as the ‘nitrate–nitrite–NO pathway’. This pathway has been reported to improve endothelial dysfunction, protect against myocardial IRI and attenuate infarct size in various experimental models. Furthermore, emerging evidence suggests that nitrite itself provides multi-faceted protection, in an NO-independent fashion, against a myriad of pathophysiologies attributed to IRI. In this review, we explore the existing pre-clinical and clinical evidence for the role of nitrate and nitrite in cardioprotection and discuss the lessons learnt from the clinical trials for nitrite as a perconditioning agent. We also discuss the potential future for nitrite as a pre-conditioning intervention in man.

尽管技术和治疗取得了重大进展，但心血管疾病仍然是全球死亡的主要原因，其中冠心病 (CHD) 是一个关键因素。急性心肌梗死 (AMI) 后，必须迅速恢复缺血心肌的血流。然而，这种恢复与额外并发症和进一步心肌细胞死亡的风险增加有关，称为心肌缺血再灌注损伤 (IRI)。内源性产生的一氧化氮 (NO) 在保护心肌免受 IRI 影响中起重要作用。众所周知，NO 通过“经典”NO-sGC-cGMP 途径介导其许多下游功能，这对心血管稳态至关重要；然而，当必要的底物输送不足时，该途径可能会受到损害，特别是 L-精氨酸、氧和还原当量。最近，研究表明，在缺血条件下，存在一种生成 NO 的替代途径，这已被称为“硝酸盐-亚硝酸盐-NO 途径”。据报道，该途径在各种实验模型中可改善内皮功能障碍、防止心肌 IRI 并减轻梗塞面积。此外，新出现的证据表明，亚硝酸盐本身以不依赖 NO 的方式提供了多方面的保护作用，以对抗由 IRI 引起的无数病理生理学。在这篇综述中，我们探讨了硝酸盐和亚硝酸盐在心脏保护中作用的现有临床前和临床证据，并讨论了从亚硝酸盐作为预处理剂的临床试验中吸取的经验教训。