Department of Pulmonary, Allergy and Critical Care Medicine, Respiratory Institute, Cleveland Clinic, Cleveland, OH, United States of America.
Pathobiology Division, Lerner Research Institute, Cleveland Clinic, OH, United States of America.
PLoS One. 2019 Aug 30;14(8):e0221777. doi: 10.1371/journal.pone.0221777. eCollection 2019.
Inhaled nitric oxide (NO) exerts a variety of effects through metabolites and these play an important role in regulation of hemodynamics in the body. A detailed investigation into the generation of these metabolites has been overlooked.
We investigated the kinetics of nitrite and S-nitrosothiol-hemoglobin (SNO-Hb) in plasma derived from inhaled NO subjects and how this modifies the cutaneous microvascular response.
We enrolled 15 healthy volunteers. Plasma nitrite levels at baseline and during NO inhalation (15 minutes at 40 ppm) were 102 (86-118) and 114 (87-129) nM, respectively. The nitrite peak occurred at 5 minutes of discontinuing NO (131 (104-170) nM). Plasma nitrate levels were not significantly different during the study. SNO-Hb molar ratio levels at baseline and during NO inhalation were 4.7E-3 (2.5E-3-5.8E-3) and 7.8E-3 (4.1E-3-13.0E-3), respectively. Levels of SNO-Hb continued to climb up to the last study time point (30 min: 10.6E-3 (5.3E-3-15.5E-3)). The response to acetylcholine iontophoresis both before and during NO inhalation was inversely associated with the SNO-Hb level (r: -0.57, p = 0.03, and r: -0.54, p = 0.04, respectively).
Both nitrite and SNO-Hb increase during NO inhalation. Nitrite increases first, followed by a more sustained increase in Hb-SNO. Nitrite and Hb-SNO could be a mobile reservoir of NO with potential implications on the systemic microvasculature.
吸入一氧化氮（NO）通过代谢物发挥多种作用，这些代谢物在调节体内血液动力学方面起着重要作用。对这些代谢物的生成进行详细研究一直被忽视。
我们研究了吸入 NO 后血浆中亚硝酸盐和 S-亚硝基血红蛋白（SNO-Hb）的动力学，以及这如何改变皮肤微血管反应。
我们招募了 15 名健康志愿者。基础状态和吸入 NO（40ppm 15 分钟）时的血浆亚硝酸盐水平分别为 102（86-118）和 114（87-129）nM。NO 停止后 5 分钟亚硝酸盐达到峰值（131（104-170）nM）。研究过程中血浆硝酸盐水平无显著差异。基础状态和吸入 NO 时的 SNO-Hb 摩尔比水平分别为 4.7E-3（2.5E-3-5.8E-3）和 7.8E-3（4.1E-3-13.0E-3）。SNO-Hb 水平持续升高，直至最后一个研究时间点（30min：10.6E-3（5.3E-3-15.5E-3））。在吸入 NO 前后，乙酰胆碱离子电渗法的反应与 SNO-Hb 水平呈负相关（r：-0.57，p=0.03，和 r：-0.54，p=0.04）。
吸入 NO 期间，亚硝酸盐和 SNO-Hb 均增加。亚硝酸盐先增加，随后 Hb-SNO 持续增加。亚硝酸盐和 Hb-SNO 可能是 NO 的移动储存库，对全身微血管系统具有潜在影响。
