Dept. of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Dept. of Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden.
Dept. of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Nitric Oxide. 2018 May 1;75:16-26. doi: 10.1016/j.niox.2018.02.001. Epub 2018 Feb 8.
Numerous studies have shown beneficial cardiovascular and metabolic effects of dietary nitrate but the release or uptake of these anions on an organ level is still poorly elucidated. Here we administered sodium nitrate in the pig and measured acute changes in release/uptake of nitrate and nitrite across several organs as well as cardiovascular and metabolic functions. In 17 anesthetized pigs multiple venous catheters and arterial ultrasonic blood flow probes were positioned. After pretreatment with the NO synthase (NOS) inhibitor l-NAME to minimize involvement of NOS-dependent nitrate/nitrite generation, the animals received bolus injections of either sodium nitrate or sodium chloride. Organ blood flows and release/uptake of nitrate and nitrite were measured in the pulmonary, splanchnic, hepatic and renal circulations for up to two hours. In addition, small intestinal luminal NO, gut secretion of nitrate, as well as hepatic and renal NADPH oxidase activity were measured. At baseline there was a significant uptake of nitrite in the liver and kidneys together with a release of nitrite from the lungs. In the control pigs, arterial plasma nitrite progressively declined during the observation period (-54%) but was stable in the nitrate group, indicating conversion of nitrate to nitrite. Sodium nitrate led to a marked accumulation of nitrate in the small intestinal lumen with a parallel increase in luminal nitrite. This was coupled with release of nitrite in the portal vein and a concomitant uptake of this anion in the liver. There was a trend towards reduced NADPH oxidase-dependent superoxide generation in the liver but an increase in the kidney. Nitrate had no acute effects on cardiovascular parameters or regional and systemic oxygen consumption. In conclusion, we found a notable difference in release and uptake of nitrate and nitrite between the organs investigated. Our findings indicate an acute conversion of nitrate to nitrite, most likely independent of oral bacteria but by a mammalian nitrate reductase and/or gut bacteria.
许多研究表明，饮食硝酸盐对心血管和代谢有有益影响，但这些阴离子在器官水平上的释放或摄取仍不清楚。在这里，我们在猪身上给予硝酸钠，并测量了硝酸盐和亚硝酸盐在几个器官中的急性释放/摄取以及心血管和代谢功能的变化。在 17 头麻醉猪身上，放置了多个静脉导管和动脉超声血流探头。在用一氧化氮合酶（NOS）抑制剂 l-NAME 预处理以尽量减少 NOS 依赖的硝酸盐/亚硝酸盐生成的参与后，动物接受了硝酸钠或氯化钠的推注注射。在肺、内脏、肝和肾循环中测量了硝酸盐和亚硝酸盐的器官血流和释放/摄取，持续长达两小时。此外，还测量了小肠腔中的 NO、硝酸盐的肠道分泌以及肝和肾 NADPH 氧化酶活性。在基线时，肝脏和肾脏中存在明显的亚硝酸盐摄取，同时从肺部释放亚硝酸盐。在对照猪中，动脉血浆中亚硝酸盐在观察期间逐渐下降（-54%），但在硝酸盐组中稳定，表明硝酸盐转化为亚硝酸盐。硝酸钠导致小肠腔中硝酸盐的明显积累，同时腔中亚硝酸盐增加。这与门静脉中亚硝酸盐的释放和肝脏中对该阴离子的摄取相耦合。肝中 NADPH 氧化酶依赖性超氧化物生成呈减少趋势，但肾中增加。硝酸盐对心血管参数或局部和全身耗氧量没有急性影响。总之，我们发现研究的器官之间在硝酸盐和亚硝酸盐的释放和摄取方面存在显著差异。我们的研究结果表明硝酸盐急性转化为亚硝酸盐，很可能独立于口腔细菌，但由哺乳动物硝酸盐还原酶和/或肠道细菌介导。
