William Harvey Research Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, London, UK.
Departamento de Farmacologia, Federal University of Santa Catarina, Florianópolis, Brazil.
Br J Pharmacol. 2022 Oct;179(20):4757-4777. doi: 10.1111/bph.15636. Epub 2021 Oct 6.
NO is a vasodilator and independent modulator of cardiac remodelling. Commonly, in cardiac disease (e.g., heart failure), endothelial dysfunction (synonymous with NO deficiency) has been implicated in increased BP, cardiac hypertrophy and fibrosis. Currently, no effective therapies replacing NO have succeeded in the clinic. Inorganic nitrate (NO ), through chemical reduction to nitrite and then to NO, exerts potent BP lowering, but whether it might be useful in treating undesirable cardiac remodelling is not known.
We analysed demographics in a nested age- and sex-matched case-control study of hypertensive patients with or without left ventricular hypertrophy (NCT03088514) and assessed the effects of dietary nitrate in mouse models of cardiac dysfunction.
Lower plasma nitrite concentrations and vascular dysfunction accompanied cardiac hypertrophy and fibrosis in patients. In mouse models of cardiac remodelling, restoration of circulating nitrite levels using dietary nitrate improved endothelial dysfunction through targeting the xanthine oxidoreductase-driven increase in levels of H O and superoxide, and decreased cardiac fibrosis through NO-mediated block of SMAD phosphorylation leading to improvements in cardiac structure and function.
Dietary nitrate offers easily translatable therapeutic options for delivery of NO and thereby treatment of cardiac dysfunction.
一氧化氮（NO）是一种血管扩张剂，也是心脏重构的独立调节剂。通常，在心脏疾病（如心力衰竭）中，内皮功能障碍（与 NO 缺乏同义）与血压升高、心脏肥大和纤维化有关。目前，尚无替代 NO 的有效疗法在临床上取得成功。无机硝酸盐（NO ）通过化学还原为亚硝酸盐，然后再转化为 NO，可有效降低血压，但它是否可用于治疗不良的心脏重构尚不清楚。
我们在一项高血压患者伴或不伴左心室肥厚的年龄和性别匹配巢式病例对照研究中分析了人口统计学数据（NCT03088514），并评估了饮食硝酸盐在心脏功能障碍小鼠模型中的作用。
较低的血浆亚硝酸盐浓度和血管功能障碍伴随着患者的心脏肥大和纤维化。在心脏重构的小鼠模型中，通过饮食硝酸盐恢复循环中的亚硝酸盐水平可通过靶向黄嘌呤氧化还原酶驱动的 H 2 O 2 和超氧化物水平升高来改善内皮功能障碍，并通过 NO 介导的 SMAD 磷酸化阻断来减少心脏纤维化，从而改善心脏结构和功能。
饮食硝酸盐为提供 NO 的可转化治疗选择提供了机会，从而可治疗心脏功能障碍。
