Contribution of membrane permeability and unstirred layer diffusion to nitric oxide-red blood cell interaction.
Contribution of membrane permeability and unstirred layer diffusion to nitric oxide-red blood cell interaction.
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DOI：
10.1016/j.jtbi.2012.10.025
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发表时间：
2013-01-21
影响因子：
2
通讯作者：
Kavdia, Mahendra
中科院分区：
文献类型：
--
作者：
Deonikar, Prabhakar;Kavdia, Mahendra
一氧化氮（NO）在血管系统中被红细胞（RBC）血红蛋白（Hb）消耗在调节血管张力中是至关重要的。与游离Hb相比，由于转运阻力，包括膜阻力、NO生物转运至RBC的细胞外和细胞内阻力，RBC对NO的消耗较低，从而减轻了在RBC中靠近有效NO清除剂Hb的内皮处产生NO的矛盾。各转运阻力对NO-RBC相互作用的相对贡献尚不清楚。通过分析红细胞膜通透性（Pm）、红细胞压积（Hct）和NO-Hb反应速率常数对NO-RBC相互作用的影响，建立了一个NO向单个红细胞转运的数学模型，以量化单个转运屏障的贡献。我们的研究结果表明，细胞内扩散的NO是不是一个速率限制步骤的NO-红细胞相互作用。对于Pm >1 cm/s，细胞外扩散贡献了总转运阻力的70-90%，而对于Pm < 0.1 cm/s，膜阻力占总转运阻力的50-75%。我们提出了一个狭窄的Pm范围为0.21-0.44厘米/秒，分别为10-45%的红细胞压积，低于膜阻力是更显着的，高于细胞外扩散是一个主要的运输阻力NO-红细胞相互作用。
Nitric oxide (NO) consumption by red blood cell (RBC) hemoglobin (Hb) in vasculature is critical in regulating the vascular tone. The paradox of NO production at endothelium in close proximity of an effective NO scavenger Hb in RBCs is mitigated by lower NO consumption by RBCs compared to that of free Hb due to transport resistances including membrane resistance, extra- and intra- cellular resistances for NO biotransport to the RBC. Relative contribution of each transport resistance on NO-RBC interactions is still not clear. We developed a mathematical model of NO transport to a single RBC to quantify the contributions from individual transport barriers by analyzing the effect of RBC membrane permeability (Pm), hematocrit (Hct) and NO-Hb reaction rate constants on NO-RBC interactions. Our results indicated that intracellular diffusion of NO was not a rate limiting step for NO-RBC interactions. The extracellular diffusion contributed 70–90% of total transport resistance for Pm >1 cm/s whereas membrane resistance accounts for 50–75% of total transport resistance for Pm < 0.1 cm/s. We propose a narrow Pm range of 0.21–0.44 cm/s for 10–45% Hct, respectively, below which membrane resistance is more significant and above which extracellular diffusion is a dominating transport resistance for NO-RBC interactions.
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