A computational model for nitric oxide, nitrite and nitrate biotransport in the microcirculation: effect of reduced nitric oxide consumption by red blood cells and blood velocity.

A computational model for nitric oxide, nitrite and nitrate biotransport in the microcirculation: effect of reduced nitric oxide consumption by red blood cells and blood velocity.
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DOI:
10.1016/j.mvr.2010.09.004
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发表时间:
2010-12
影响因子:
3.1
通讯作者:
Kavdia M
Kavdia M
中科院分区:
医学3区
文献类型:
--
作者:
Deonikar P;Kavdia M

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血管中血管活性内皮衍生一氧化氮(NO)的生物利用度是许多生理过程调节的关键因素。红细胞对NO的消耗在维持NO生物利用度方面起着至关重要的作用。最近,Deonikar等人报道了一个有效的NO - 红细胞反应速率常数为0.2×10⁵ M⁻¹s⁻¹,比常用的NO - 红细胞反应速率常数1.4×10⁵ M⁻¹s⁻¹低约7倍。为了研究较低的NO - 红细胞反应速率常数以及亚硝酸盐和硝酸盐形成(血液中NO代谢产物)的影响,我们建立了一个内径为50和200μm的小动脉中NO生物转运的二维数学模型,以计算小动脉血管腔和血管壁径向和轴向的NO浓度。我们还模拟了血流速度对小动脉中NO分布的影响,以确定NO是否能够被运输到小动脉腔的下游位置。结果表明,降低NO - 红细胞反应速率常数会增加血管腔以及血管壁中的NO浓度。增加血流速度也会导致NO浓度升高。我们预测随着血流速度的增加,轴向的NO浓度梯度会增加。对于内径为50μm的小动脉,在血流速度为0.5 - 4 cm/s且kNO - RBC为0.2×10⁵ M⁻¹s⁻¹的情况下,平滑肌细胞层中预测的NO浓度为281 - 1163 nM,这比早期数学建模研究报道的值高得多。该NO浓度与在几个不同血管床中实验测量的血管壁NO浓度范围300 - 1000 nM相似。从NO在适当条件下可能向下游运输的角度来看,这些结果具有重要意义。
Bioavailability of vasoactive endothelium-derived nitric oxide (NO) in vasculature is a critical factor in regulation of many physiological processes. Consumption of NO by RBC plays a crucial role in maintaining NO bioavailability. Recently, Deonikar et al reported a effective NO-RBC reaction rate constant of 0.2×105 M−1s−1 that is ~7 times lower than the commonly used NO-RBC reaction rate constant of 1.4×105 M−1s−1. To study the effect of lower NO-RBC reaction rate constant and nitrite and nitrate formation (products of NO metabolism in blood), we developed a 2D mathematical model of NO biotransport in 50 and 200 μm ID arterioles to calculate NO concentration in radial and axial direction in the vascular lumen and vascular wall of the arterioles. We also simulated the effect of blood velocity on NO distribution in the arterioles to determine whether NO can be transported to downstream locations in the arteriolar lumen. The results indicate that lowering the NO-RBC reaction rate constant increased the NO concentration in the vascular lumen as well as the vascular wall. Increasing the velocity also led to increase in NO concentration. We predict increased NO concentration gradient along the axial direction with an increase in the velocity. The predicted NO concentration were 281–1163 nM in the smooth muscle cell layer for 50 μm arteriole over the blood velocity range of 0.5–4 cm/s for kNO-RBC of 0.2×105 M−1 s−1, which are much higher than the reported values from earlier mathematical modeling studies. The NO concentrations are similar to the experimentally measured vascular wall NO concentration range of 300–1000 nM in several different vascular beds. The results are significant from the perspective that the downstream transport of NO is possible under right circumstances.
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