Extracellular diffusion and permeability effects on NO-RBCs interactions using an experimental and theoretical model.
Extracellular diffusion and permeability effects on NO-RBCs interactions using an experimental and theoretical model.
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DOI：
10.1016/j.mvr.2009.10.002
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发表时间：
2010-01
影响因子：
3.1
通讯作者：
Kavdia M
中科院分区：
文献类型：
--
作者：
Deonikar P;Kavdia M
一氧化氮（NO）是一种有效的血管扩张剂，其体内平衡依赖于与红细胞的相互作用。了解血管腔中NO-RBC相互作用的关键因素是对产物鉴定和定量的综合分析。在这种情况下，在体外NO-红细胞相互作用过程中NO的管理成为一个至关重要的变量。在这项研究中，我们设计了一个生物反应器，保持一个精确的NO浓度的顶部空间，扩散到红细胞悬浮液中，研究NO浓度和红细胞压积（Hct）对NO-红细胞相互作用的定量影响。通过化学发光法测定NO-RBC反应产物（亚硝酸盐和总氮物质（总NOx））。建立了一个模拟NO向单个红细胞生物转运的数学模型，用于：1）估算NO-红细胞反应速率常数; 2）预测红细胞膜NO渗透性（Pm）值为0.0415-40 cm/s时，红细胞悬浮液和红细胞膜上的NO浓度。测得的亚硝酸盐和总氮氧化物浓度增加，而在顶部空间NO浓度的增加，亚硝酸盐浓度下降，红细胞压积和总氮氧化物浓度增加，红细胞压积。这表明细胞外阻力是红细胞摄取NO的控制因素。建模结果表明，NO-RBC相互作用的有效反应速率常数（keff）为2.32 × 104 - 1.08 × 106 M−1 s−1。结果还预测，需要在0.0415 - 0.4 cm/s范围内的膜渗透性来维持平滑肌细胞层处的NO的生理相关水平。有效反应速率常数随着Pm的增加而增加，并且在45%Hct时增加的幅度更高。对于所有Pm值，与5%Hct相比，45%Hct的khb/keff比率较低，表明细胞外阻力对于RBC NO摄取是重要的。我们的实验和数学分析的NO-红细胞相互作用表明，无搅拌层和红细胞膜有显着的影响NO运输到红细胞。此外，需要在0.0415 - 0.4 cm/s范围内的膜渗透性以在平滑肌细胞层维持足够的NO浓度。
Nitric oxide (NO) is a potent vasodilator and its homeostasis depends on interaction with RBCs. A key factor in understanding NO-RBC interactions in vascular lumen is a comprehensive analysis of product identification and quantification. In this context, administration of NO during in vitro NO-RBC interactions becomes a crucial variable. In this study, we designed a bioreactor that maintains a precise NO concentration in the headspace that diffuses to RBCs suspension to study the quantitative effect of NO concentration and hematocrit (Hct) on NO-RBC interactions. The products of NO-RBC reaction (nitrite and total nitrogen species (total NOx)) were measured by chemiluminescence assay. A mathematical model simulating NO biotransport to a single RBC was developed to 1) estimate NO-RBC reaction rate constant; 2) predict the NO concentrations in the bulk RBC suspension and at the RBC membrane for RBC membrane NO permeability (Pm) values of 0.0415–40 cm/s. Measured nitrite and total NOx concentrations increased with increase in headspace NO concentration whereas nitrite concentrations decreased with hematocrit and total NOx concentrations increased with hematocrit. This indicates that the extracellular resistance is a controlling factor for RBC uptake of NO. Modeling results showed that the effective reaction rate constant (keff) for NO-RBC interactions was 2.32 × 104 – 1.08 × 106 M−1 s−1. Results also predict that the membrane permeability in the range of 0.0415 – 0.4 cm/s is required to maintain physiologically relevant levels of NO at the smooth muscle cell layer. The effective reaction rate constant increased with increase in Pm and magnitude of increase was higher at 45% Hct. For all Pm values, the khb/keff ratios were lower for 45% Hct as compared to 5% Hct indicating extracellular resistance is important for RBC NO uptake. Our experimental and mathematical analyses of NO-RBC interactions indicate that both unstirred layer and RBC membrane have a significant effect on NO transport to RBCs. In addition, the membrane permeability in the range of 0.0415 – 0.4 cm/s is required to maintain sufficient NO concentrations at the smooth muscle cell layer.
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DOI：
10.1073/pnas.74.8.3203
发表时间：
1977-01-01
影响因子：
11.1
作者：
ARNOLD, WP;MITTAL, CK;MURAD, F
通讯作者：
MURAD, F
DOI：
10.1073/pnas.152149699
发表时间：
2002-08-06
影响因子：
11.1
作者：
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影响因子：
7.4
作者：
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影响因子：
3.8
作者：
CARLSEN, E;COMROE, JH
通讯作者：
COMROE, JH
影响因子：
3.8
作者：
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