PHARMACODYNAMICS OF PLASMA NITRATE/NITRITE AS AN INDICATION OF NITRIC-OXIDE FORMATION IN CONSCIOUS DOGS
PHARMACODYNAMICS OF PLASMA NITRATE/NITRITE AS AN INDICATION OF NITRIC-OXIDE FORMATION IN CONSCIOUS DOGS
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DOI：
10.1161/01.cir.91.12.2982
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发表时间：
1995-06-15
期刊：
影响因子：
37.8
通讯作者：
HINTZE, TH
中科院分区：
文献类型：
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作者：
ZEBALLOS, GA;BERNSTEIN, RD;HINTZE, TH
背景 本研究是为了更好地了解体内一氧化氮 (NO) 的产生，通过实验动物研究或人类临床研究血液样本中血浆亚硝酸盐或硝酸盐的变化来测量。方法和结果血浆样本取自长期接受仪器检测的清醒狗的主动脉、冠状窦、腿部外周静脉（骨骼肌）或右心室（混合静脉）。使用盐酸在氩气环境中将血浆亚硝酸盐转化为NO气体，并且首先用硝酸还原酶将血浆硝酸盐转化为亚硝酸盐，然后用酸将血浆硝酸盐转化为NO气体。构建标准曲线，并测定血浆中亚硝酸盐和硝酸盐的量。主要代谢物是硝酸盐，而亚硝酸盐约占总量的 10%，且保持不变。在休息的狗中，唯一具有正动静脉硝酸盐差异的血管床是心脏，这是产生一氧化氮的证据。给安静休息的狗输注硝酸盐会导致血浆硝酸盐增加至38 +/- 3.4 mmol/L，全身动脉压增加，并产生明显的利尿作用。血浆半衰期计算为3.8小时。分布体积计算为 0.215 L/kg，或相当于细胞外体积。 结论 这些研究表明硝酸盐是体内 NO 代谢的可靠指标，但由于半衰期长，硝酸盐一旦产生就会在血浆中积累。由于分布体积较大（体重的 21% 与通常归因于血浆体积（测量硝酸盐的隔室）的体重的 4%），血浆硝酸盐的简单测量会低估身体实际产生的硝酸盐或一氧化氮的 4 至 6 倍。在心力衰竭等肾功能和细胞外容量发生改变的疾病状态下，当评估血浆中硝酸盐的增加作为 NO 形成的指标时，应谨慎行事。
Background The present investigation was undertaken to better understand the production of nitric oxide (NO) in vivo as measured by alterations in plasma nitrite or nitrate in blood samples from studies in experimental animals or clinical studies in humans.Methods and Results Plasma samples were taken from the aorta, the coronary sinus, a peripheral vein in the leg (skeletal muscle), or the right ventricle (mixed venous) in chronically instrumented conscious dogs. Plasma nitrite was converted to NO gas in an argon environment by use of hydrochloric acid, and plasma nitrate was converted first to nitrite with nitrate reductase and then to NO gas with acid. Standard curves were constructed, and the amount of nitrite and nitrate in plasma was determined. The primary metabolite was nitrate, whereas nitrite was approximately 10% of the total and remained constant. In the resting dog, the only vascular bed with a positive arterial-venous nitrate difference, evidence for production of NO, was the heart. Nitrate infusion into quietly resting dogs resulted in increases in plasma nitrate up to 38 +/- 3.4 mmol/L, increases in systemic arterial pressure, and a marked diuresis. The plasma half-life was calculated as 3.8 hours. The volume of distribution was calculated as 0.215 L/kg, or equivalent to the extracellular volume.Conclusions These studies indicate that nitrate is a reliable measure of NO metabolism in vivo but that because of the long half-life, nitrate will accumulate in plasma once it is produced. Because of the large volume of distribution (21% of body weight versus the 4% of body weight usually attributed to plasma volume, the compartment in which nitrate is measured), simple measures of plasma nitrate underestimate by a factor of 4 to 6 the actual production of nitrate or NO by the body. In disease states, such as heart failure, in which renal function and extracellular volume are altered, caution should be exercised when increases in nitrate in plasma as an index of NO formation are evaluated.