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Direct comparison of inorganic nitrite and nitrate on vascular dysfunction and oxidative damage in experimental arterial hypertension
Nitric Oxide ( IF 3.9 ) Pub Date : 2021-06-04 , DOI: 10.1016/j.niox.2021.06.001
Paul Stamm 1 , Matthias Oelze 2 , Sebastian Steven 2 , Swenja Kröller-Schön 2 , Miroslava Kvandova 2 , Sanela Kalinovic 2 , Agnieszka Jasztal 3 , Agnieszka Kij 3 , Marin Kuntic 2 , Maria Teresa Bayo Jimenez 2 , Bartosz Proniewski 3 , Huige Li 4 , Eberhard Schulz 5 , Stefan Chlopicki 6 , Andreas Daiber 1 , Thomas Münzel 1
Affiliation  

Arterial hypertension is one of the major health risk factors leading to coronary artery disease, stroke or peripheral artery disease. Dietary uptake of inorganic nitrite (NO2) and nitrate (NO3) via vegetables leads to enhanced vascular NO bioavailability and provides antihypertensive effects. The present study aims to understand the underlying vasoprotective effects of nutritional NO2 and NO3 co-therapy in mice with angiotensin-II (AT-II)-induced arterial hypertension. High-dose AT-II (1 mg/kg/d, 1w, s. c.) was used to induce arterial hypertension in male C57BL/6 mice. Additional inorganic nitrite (7.5 mg/kg/d, p. o.) or nitrate (150 mg/kg/d, p. o.) were administered via the drinking water. Blood pressure (tail-cuff method) and endothelial function (isometric tension) were determined. Oxidative stress and inflammation markers were quantified in aorta, heart, kidney and blood. Co-treatment with inorganic nitrite, but not with nitrate, normalized vascular function, oxidative stress markers and inflammatory pathways in AT-II treated mice. Of note, the highly beneficial effects of nitrite on all parameters and the less pronounced protection by nitrate, as seen by improvement of some parameters, were observed despite no significant increase in plasma nitrite levels by both therapies. Methemoglobin levels tended to be higher upon nitrite/nitrate treatment. Nutritional nitric oxide precursors represent a non-pharmacological treatment option for hypertension that could be applied to the general population (e.g. by eating certain vegetables). The more beneficial effects of inorganic nitrite may rely on superior NO bioactivation and stronger blood pressure lowering effects. Future large-scale clinical studies should investigate whether hypertension and cardiovascular outcome in general can be influenced by dietary inorganic nitrite therapy.



中文翻译:

无机亚硝酸盐和硝酸盐对实验性动脉高血压血管功能障碍和氧化损伤的直接比较

动脉高血压是导致冠状动脉疾病、中风或外周动脉疾病的主要健康风险因素之一。通过蔬菜摄入无机亚硝酸盐 (NO 2 - ) 和硝酸盐 (NO 3 - ) 可提高血管 NO 的生物利用度并提供抗高血压作用。本研究旨在了解营养 NO 2 -和 NO 3 -的潜在血管保护作用血管紧张素-II(AT-II)诱导的动脉高血压小鼠的联合治疗。高剂量 AT-II (1 mg/kg/d, 1w, sc) 用于诱导雄性 C57BL/6 小鼠的动脉高血压。通过饮用水给予额外的无机亚硝酸盐(7.5 mg/kg/d,口服)或硝酸盐(150 mg/kg/d,口服)。测定血压(尾套法)和内皮功能(等长张力)。对主动脉、心脏、肾脏和血液中的氧化应激和炎症标志物进行了量化。在 AT-II 治疗的小鼠中,与无机亚硝酸盐共同治疗,但不与硝酸盐共同治疗,使血管功能、氧化应激标志物和炎症通路正常化。值得注意的是,亚硝酸盐对所有参数的非常有益的影响和硝酸盐的不太明显的保护作用,从一些参数的改进可以看出,尽管两种疗法均未显着增加血浆亚硝酸盐水平,但仍观察到。亚硝酸盐/硝酸盐处理后,高铁血红蛋白水平往往更高。营养性一氧化氮前体代表了一种可应用于一般人群的非药物治疗高血压(例如通过食用某些蔬菜)。无机亚硝酸盐的更有益作用可能依赖于卓越的 NO 生物活化作用和更强的降血压作用。未来的大规模临床研究应调查饮食无机亚硝酸盐治疗是否会影响高血压和心血管结局。营养性一氧化氮前体代表了一种可应用于一般人群的非药物治疗高血压(例如通过食用某些蔬菜)。无机亚硝酸盐的更有益作用可能依赖于卓越的 NO 生物活化作用和更强的降血压作用。未来的大规模临床研究应调查饮食无机亚硝酸盐治疗是否会影响高血压和心血管结局。营养性一氧化氮前体代表了一种可应用于一般人群的非药物治疗高血压(例如通过食用某些蔬菜)。无机亚硝酸盐的更有益作用可能依赖于卓越的 NO 生物活化作用和更强的降血压作用。未来的大规模临床研究应调查饮食无机亚硝酸盐治疗是否会影响高血压和心血管结局。

更新日期:2021-06-11
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