Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Av. Bandeirantes, 3900, 14049-900, Ribeirao Preto, SP, Brazil.
Department of Chemisty, Faculty of Phylosophy, Sciences and Languages of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes 3900, 14040-901, Ribeirao Preto, SP, Brazil.
Nitric Oxide. 2018 Apr 1;74:65-73. doi: 10.1016/j.niox.2018.01.006.
Nitrite reduces blood pressure (BP) in both clinical and experimental hypertension. This effect is attributable to the formation of nitric oxide (NO) and other NO-related species, which may be improved by ascorbate or other antioxidants. However, the BP responses to oral nitrite result, at least in part, of increased gastric S-nitrosothiol formation. This study tested the hypothesis that ascorbate may destroy S-nitrosothiols and therefore not all doses of ascorbate enhance the BP responses to oral nitrite. We assessed the BP responses to oral sodim nitrite (0.2 mmol/kg) in L-NAME hypertensive rats pretreated with ascorbate (0, 0.02, 0.2, or 2 mmol/kg). Plasma and gastric wall concentrations of nitrite and nitroso compounds concentrations were determined using an ozone-based reductive chemiluminescence assay. Nitrate concentrations were determined using the Griess reaction. Free thiol concentrations were determined by a colorimetric assay. The BP responses to nitrite exhibited a bell-shape profile as they were not modified by ascorbate 0.02 mmol/l, whereas the 0.2 mmol/kg dose enhanced and the 2 mmol/kg dose attenuated BP responses. In parallel with BP responses, nitrite-induced increases in plasma nitrite and RSNO species were not modified by ascorbate 0.02 mmol/l, whereas the 0.2 mmol/kg dose enhanced and the 2 mmol/kg dose attenuated them. Similar experiments were carried out with an equimolar dose of S-nitrosogluthathione. Ascorbate dose-dependently impaired the BP responses to S-nitrosogluthathione, and the corresponding increases in plasma RSNO, but not in plasma nitrite concentrations. This is the first study to show that while ascorbate dose-dependently impairs the BP responses to oral S-nitrosogluthathione, there are contrasting effects when low versus high ascorbate doses are compared with respect to its effects on the blood pressure responses to oral nitrite administration. Our findings may have special implications to patients taking ascorbate, as high doses of this vitamin may impair protective mechanisms associated with nitrite or nitrate from dietary sources.
亚硝酸盐可降低临床和实验性高血压患者的血压。这种作用归因于一氧化氮（NO）和其他与 NO 相关的物质的形成，而抗坏血酸或其他抗氧化剂可能会改善这些物质的形成。然而，口服亚硝酸盐引起的血压反应至少部分归因于胃 S-亚硝基硫醇形成的增加。本研究检验了这样一个假设，即抗坏血酸可能会破坏 S-亚硝基硫醇，因此并非所有剂量的抗坏血酸都会增强口服亚硝酸盐引起的血压反应。我们评估了预先给予抗坏血酸（0、0.02、0.2 或 2 mmol/kg）的 L-NAME 高血压大鼠口服 sodim 亚硝酸盐（0.2 mmol/kg）的血压反应。使用基于臭氧的还原性化学发光测定法测定血浆和胃壁中亚硝酸盐和硝基化合物浓度。使用格里斯反应测定硝酸盐浓度。通过比色法测定游离巯基浓度。血压反应呈钟形曲线，抗坏血酸 0.02 mmol/l 不改变血压反应，而 0.2 mmol/kg 剂量增强，2 mmol/kg 剂量减弱。与血压反应平行，亚硝酸盐诱导的血浆亚硝酸盐和 RSNO 物种增加不受抗坏血酸 0.02 mmol/l 影响，而 0.2 mmol/kg 剂量增强，2 mmol/kg 剂量减弱。用等摩尔剂量的 S-亚硝基谷胱甘肽进行了类似的实验。抗坏血酸剂量依赖性地损害了对 S-亚硝基谷胱甘肽的血压反应，以及相应的血浆 RSNO 增加，但血浆亚硝酸盐浓度没有增加。这是第一项表明，虽然抗坏血酸剂量依赖性地损害了口服 S-亚硝基谷胱甘肽的血压反应，但与低剂量和高剂量抗坏血酸相比，其对口服亚硝酸盐给药引起的血压反应的影响存在差异。我们的发现可能对服用抗坏血酸的患者具有特殊意义，因为这种维生素的高剂量可能会损害与饮食来源的亚硝酸盐或硝酸盐相关的保护机制。
