Effects of long-term dietary nitrate supplementation in mice

作者：Michael P. Hezel, Ming Rong Liu, Tomas A. Schiffer, Filip Jon Larsen, Antonio Checa, Craig E. Wheelock, Mattias Carlström, Jon O. Lundberg, Eddie Weitzberg · 发表于：Redox Biology · 年份：2015 · DOI：10.1016/j.redox.2015.05.004 · 被引用次数：70 · 研究领域：Nitric Oxide and Endothelin Effects、Exercise and Physiological Responses、Antioxidants, Aging, Portulaca oleracea

BACKGROUND: Inorganic nitrate (NO3(-)) is a precursor of nitric oxide (NO) in the body and a large number of short-term studies with dietary nitrate supplementation in animals and humans show beneficial effects on cardiovascular health, exercise efficiency, host defense and ischemia reperfusion injury. In contrast, there is a long withstanding concern regarding the putative adverse effects of chronic nitrate exposure related to cancer and adverse hormonal effects. To address these concerns we performed in mice, a physiological and biochemical multi-analysis on the effects of long-term dietary nitrate supplementation. DESIGN: 7 week-old C57BL/6 mice were put on a low-nitrate chow and at 20 weeks-old were treated with NaNO3 (1 mmol/L) or NaCl (1 mmol/L, control) in the drinking water. The groups were monitored for weight gain, food and water consumption, blood pressure, glucose metabolism, body composition and oxygen consumption until one group was reduced to eight animals due to death or illness. At that point remaining animals were sacrificed and blood and tissues were analyzed with respect to metabolism, cardiovascular function, inflammation, and oxidative stress. RESULTS: Animals were supplemented for 17 months before final sacrifice. Body composition, oxygen consumption, blood pressure, glucose tolerance were measured during the experiment, and vascular reactivity and muscle mitochondrial efficiency measured at the end of the experiment with no differences identified betwe...