Bryan Nathan S, Calvert John W, Gundewar Susheel, Lefer David J
The Brown Foundation Institute of Molecular Medicine, University of Texas-Houston Health Sciences Center, Houston, TX 77030, USA.
Free Radic Biol Med. 2008 Aug 15;45(4):468-74. doi: 10.1016/j.freeradbiomed.2008.04.040. Epub 2008 May 5.
Endothelial production of nitric oxide (NO) is critical for vascular homeostasis. Nitrite and nitrate are formed endogenously by the stepwise oxidation of NO and have, for years, been regarded as inactive degradation products. As a result, both anions are routinely used as surrogate markers of NO production, with nitrite as a more sensitive marker. However, both nitrite and nitrate are derived from dietary sources. We sought to determine how exogenous nitrite affects steady-state concentrations of NO metabolites thought to originate from nitric oxide synthase (NOS)-derived NO as well as blood pressure and myocardial ischemia-reperfusion (I/R) injury. Mice deficient in endothelial nitric oxide synthase (eNOS-/-) demonstrated decreased blood and tissue nitrite, nitrate, and nitroso proteins, which were further reduced by low-nitrite (NOx) diet for 1 week. Nitrite supplementation (50 mg/L) in the drinking water for 1 week restored NO homeostasis in eNOS-/- mice and protected against I/R injury. Nitrite failed to alter heart rate or mean arterial blood pressure at the protective dose. These data demonstrate the significant influence of dietary nitrite intake on the maintenance of steady-state NO levels. Dietary nitrite and nitrate may serve as essential nutrients for optimal cardiovascular health and may provide a novel prevention/treatment modality for disease associated with NO insufficiency.
内皮细胞产生一氧化氮（NO）对血管稳态至关重要。亚硝酸盐和硝酸盐由NO逐步氧化内源性生成，多年来一直被视为无活性的降解产物。因此，这两种阴离子通常被用作NO生成的替代标志物，亚硝酸盐是更敏感的标志物。然而，亚硝酸盐和硝酸盐都来源于饮食。我们试图确定外源性亚硝酸盐如何影响被认为源自一氧化氮合酶（NOS）产生的NO的NO代谢物的稳态浓度，以及血压和心肌缺血再灌注（I/R）损伤。内皮型一氧化氮合酶缺陷（eNOS-/-）小鼠的血液和组织中亚硝酸盐、硝酸盐和亚硝基化蛋白水平降低，低亚硝酸盐（NOx）饮食1周后进一步降低。饮用水中补充亚硝酸盐（50 mg/L）1周可恢复eNOS-/-小鼠的NO稳态，并预防I/R损伤。在保护剂量下，亚硝酸盐未能改变心率或平均动脉血压。这些数据表明饮食中亚硝酸盐摄入量对维持NO稳态水平有显著影响。饮食中的亚硝酸盐和硝酸盐可能是心血管健康最佳状态的必需营养素，并可能为与NO不足相关的疾病提供一种新的预防/治疗方式。
