Dietary nitrate attenuates oxidative stress, prevents cardiac and renal injuries, and reduces blood pressure in salt-induced hypertension
Dietary nitrate attenuates oxidative stress, prevents cardiac and renal injuries, and reduces blood pressure in salt-induced hypertension
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DOI：
10.1093/cvr/cvq366
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发表时间：
2011-02-01
影响因子：
10.8
通讯作者：
Lundberg, Jon O.
中科院分区：
文献类型：
--
作者：
Carlstrom, Mattias;Persson, A. Erik G.;Lundberg, Jon O.
内源性一氧化氮 (NO) 生物利用度降低是高血压和其他心血管疾病的核心病理生理事件。最近，研究表明，膳食来源的无机硝酸盐在体内转化为亚硝酸盐、NO 和其他生物活性氮氧化物。我们测试了饮食中补充无机硝酸盐可能在肾脏和心血管疾病模型中具有治疗作用的假设。 方法和结果 接受单侧肾切除术并从 3 周龄起长期接受高盐饮食的 Sprague-Dawley 大鼠出现高血压、心脏肥大和纤维化、蛋白尿以及肾损伤和氧化应激的组织学和生化迹象。同时硝酸盐治疗（0.1或1 mmol硝酸盐·kg(-1)·天(-1)），剂量较低，类似于富含蔬菜的饮食中的硝酸盐含量，可剂量依赖性地减轻高血压，且无耐受迹象。硝酸盐治疗几乎完全预防了蛋白尿和肾损伤的组织学征象，并且心脏肥大和纤维化减弱。从机制上讲，膳食硝酸盐恢复了生物活性氮氧化物的组织水平，并降低了血浆（丙二醛）和尿液（VI 类 F2-异前列腺素和 8-羟基-2-脱氧鸟苷）中氧化应激标志物的水平。此外，补充硝酸盐可使高血压大鼠循环和尿中二甲基精氨酸（ADMA 和 SDMA）水平升高正常化。结论 膳食无机硝酸盐对肾脏和心血管疾病模型具有很强的保护作用。未来的研究将揭示硝酸盐是否有助于富含蔬菜的饮食所具有的众所周知的心脏保护作用。
Aims Reduced bioavailability of endogenous nitric oxide (NO) is a central pathophysiological event in hypertension and other cardiovascular diseases. Recently, it was demonstrated that inorganic nitrate from dietary sources is converted in vivo to form nitrite, NO, and other bioactive nitrogen oxides. We tested the hypothesis that dietary inorganic nitrate supplementation may have therapeutic effects in a model of renal and cardiovascular disease.Methods and results Sprague-Dawley rats subjected to unilateral nephrectomy and chronic high-salt diet from 3 weeks of age developed hypertension, cardiac hypertrophy and fibrosis, proteinuria, and histological as well as biochemical signs of renal damage and oxidative stress. Simultaneous nitrate treatment (0.1 or 1 mmol nitrate kg(-1) day(-1)), with the lower dose resembling the nitrate content of a diet rich in vegetables, attenuated hypertension dose-dependently with no signs of tolerance. Nitrate treatment almost completely prevented proteinuria and histological signs of renal injury, and the cardiac hypertrophy and fibrosis were attenuated. Mechanistically, dietary nitrate restored the tissue levels of bioactive nitrogen oxides and reduced the levels of oxidative stress markers in plasma (malondialdehyde) and urine (Class VI F2-isoprostanes and 8-hydroxy-2-deoxyguanosine). In addition, the increased circulating and urinary levels of dimethylarginines (ADMA and SDMA) in the hypertensive rats were normalized by nitrate supplementation.Conclusion Dietary inorganic nitrate is strongly protective in this model of renal and cardiovascular disease. Future studies will reveal if nitrate contributes to the well-known cardioprotective effects of a diet rich in vegetables.