Inorganic nitrate (NO3−) and nitrate-rich foods have been shown to exert antioxidative effects and lower blood pressure in experimental animal models and human clinical studies. The specific handling of nitrate, including its enterosalivary recirculation, secretion into saliva, oral microbial reduction to nitrite (NO2−), and the pH-dependent nitrosative capacity in the stomach have all been recognized as being important for nitrate's beneficial effects. Obesity is of major health concern worldwide and associated with increased cardiovascular risk; whether nitrate lowers blood pressure and improves endothelial function in this setting has not been investigated. We here tested the hypotheses that i) nitrate elicits cardiovascular benefits in overweight women; and ii) these beneficial effects would be diminished in women who underwent bariatric Roux-en-Y gastric bypass (RYGB) surgery. Our controlled clinical trial included 15 women with prior RYGB surgery and 15 overweight female controls. All participants received a single dose of 0.1 mmol/kg/day nitrate in the form of a beetroot extract for 14 days. Blood collection, 24-h ambulatory blood pressure measurements and endothelial function tests were performed before and after nitrate treatment. Plasma nitrite, nitrate, and S-nitrosothiol (RSNO) concentrations were determined by ozone-based reductive chemiluminescence while thiobarbituric acid reactive substances (TBARS) and total antioxidant capacity (TAC) were measured using plate-reader based assays. Nitrate reduced blood pressure and improved endothelial function in controls, but not in women with prior bariatric surgery. Nitrate also increased circulating nitrate/nitrite and RSNO levels in controls, but the latter was blunted following RYGB surgery despite even larger increases in nitrite concentrations. Similarly, nitrate increased antioxidant responses in controls but not in women with prior bariatric surgery. This is the first study to show that nitrate exerts beneficial cardiovascular effects in obesity and that the morphological/functional modifications elicited by RYGB surgery abrogates nitrate's effectiveness by preventing gastric RSNO formation.

中文翻译：

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减肥手术通过干扰胃 S-亚硝基硫醇的形成来减弱硝酸盐介导的超重女性心血管功能的改善


无机硝酸盐 （NO3−） 和富含硝酸盐的食物在实验动物模型和人类临床研究中已被证明具有抗氧化作用并降低血压。硝酸盐的具体处理，包括其肠唾液再循环、分泌到唾液中、口腔微生物还原为亚硝酸盐 （NO2−） 以及胃中 pH 依赖性的亚硝化能力都被认为对硝酸盐的有益作用很重要。肥胖是世界范围内的主要健康问题，并与心血管风险增加有关;硝酸盐在这种情况下是否能降低血压和改善内皮功能尚未得到研究。我们在这里测试了以下假设：i） 硝酸盐对超重女性的心血管有益;ii） 这些有益影响在接受减肥 Roux-en-Y 胃旁路术 （RYGB） 手术的女性中会减弱。我们的对照临床试验包括 15 名既往接受过 RYGB 手术的女性和 15 名超重的女性对照。所有参与者都接受了单剂量的 0.1 mmol/kg/天甜菜根提取物形式的硝酸盐，持续 14 天。在硝酸盐处理前后进行采血、24 h 动态血压测量和内皮功能检查。血浆亚硝酸盐、硝酸盐和 S-亚硝基硫醇 （RSNO） 浓度通过基于臭氧的还原化学发光法测定，而硫代巴比妥酸反应物质 （TBARS） 和总抗氧化能力 （TAC） 使用基于读板器的测定法测量。硝酸盐可降低对照组的血压并改善内皮功能，但既往接受过减肥手术的女性则没有。 硝酸盐还增加了对照组中循环硝酸盐/亚硝酸盐和 RSNO 水平，但后者在 RYGB 手术后被减弱，尽管亚硝酸盐浓度增加幅度更大。同样，硝酸盐增加了对照组的抗氧化反应，但未增加既往减肥手术的女性的抗氧化反应。这是第一项表明硝酸盐对肥胖症产生有益心血管影响的研究，并且 RYGB 手术引起的形态/功能改变通过防止胃 RSNO 形成来消除硝酸盐的有效性。