Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, Department of Internal Medicine, Ohio State University, Columbus, OH 43210, USA.
Free Radic Biol Med. 2010 Feb 15;48(4):554-9. doi: 10.1016/j.freeradbiomed.2009.11.024. Epub 2009 Dec 4.
Endothelium-derived nitric oxide (NO) is critical in maintaining vascular tone. Accumulating evidence shows that NO bioavailability is regulated by oxygen concentration. However, it is unclear to what extent the oxygen concentration regulates NO bioavailability in the vascular wall. In this study, a recently developed experimental setup was used to measure the NO diffusion flux across the aortic wall at various oxygen concentrations. It was observed that for a constant NO concentration at the endothelial surface, the measured NO diffusion flux out of the adventitial surface at [O(2)]=0 microM is around fivefold greater than at [O(2)]=150 microM, indicating that NO is consumed in the aortic wall in an oxygen-dependent manner. Analysis of experimental data shows that the rate of NO consumption in the aortic wall is first order with respect to [NO] and first order with respect to [O(2)], and the rate constant k(1) was determined as (4.0+/-0.3) x 10(3) M(-1) s(-1). Computer simulations demonstrate that NO concentration distribution significantly changes with oxygen concentration and the effective NO diffusion distance at low oxygen level ([O(2)] < or =25 microM) is significantly longer than that at high oxygen level ([O(2)]=200 microM). These results suggest that oxygen-dependent NO consumption may play an important role in dilating blood vessels during hypoxia by increasing the effective NO diffusion distance.
内皮衍生的一氧化氮（NO）对于维持血管张力至关重要。越来越多的证据表明，NO 的生物利用度受氧浓度的调节。然而，目前尚不清楚血管壁中氧浓度在多大程度上调节 NO 的生物利用度。在这项研究中，使用了一种新开发的实验装置来测量在不同氧浓度下穿过主动脉壁的 NO 扩散通量。结果表明，对于内皮表面的恒定 NO 浓度，在 [O2] = 0 microM 时测量的从血管外膜表面逸出的 NO 扩散通量约为 [O2] = 150 microM 时的五倍，表明 NO 以氧依赖的方式在主动脉壁中被消耗。对实验数据的分析表明，主动脉壁中 NO 的消耗速率与 [NO] 呈一级关系，与 [O2] 呈一级关系，速率常数 k1 确定为（4.0+/-0.3) x 10(3) M(-1) s(-1)。计算机模拟表明，NO 浓度分布随氧浓度显著变化，低氧水平（[O2] <= 25 microM）下的有效 NO 扩散距离明显长于高氧水平（[O2] = 200 microM）。这些结果表明，氧依赖性的 NO 消耗可能通过增加有效 NO 扩散距离在缺氧期间扩张血管中发挥重要作用。
