Vascular smooth muscle NO exposure from intraerythrocytic SNOHb: A mathematical model
Vascular smooth muscle NO exposure from intraerythrocytic SNOHb: A mathematical model
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DOI：
10.1089/ars.2007.1594
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发表时间：
2007-08-01
影响因子：
6.6
通讯作者：
Popel, Aleksander S.
中科院分区：
文献类型：
--
作者：
Chen, Kejing;Pittman, Roland N.;Popel, Aleksander S.
我们之前基于不同一氧化氮（NO）合酶异构体的生化途径分析构建了计算模型，并发现我们的预测与血管周围NO测量之间存在很大差异，这表明存在非酶促NO来源。S-亚硝基血红蛋白（SNOHb）被认为是小动脉腔内释放一氧化氮并诱导缺氧血管舒张的主要来源。在本研究中，当红细胞内SNOHb释放的NO是血管中唯一的NO来源时，我们建立了一个多细胞计算模型来量化NO在小动脉平滑肌中的暴露。我们的计算表明，在平滑肌区域，一氧化氮暴露量约为0.25-6 pM。这个数字并不能解释我们在血管周围NO水平上遇到的巨大差异。我们还发现，SNOHb传递到平滑肌的NO的数量强烈依赖于SNOHb的浓度和半衰期，这进一步决定了NO的释放速度，以及红细胞（rbc）对NO的膜通透性。总之，我们的数学模型预测，皮摩尔量的NO可以通过红细胞内SNOHb传递到血管平滑肌；单凭这个量的NO似乎不足以诱导缺氧血管舒张。
We previously constructed computational models based on the biochemical pathway analysis of different nitric oxide (NO) synthase isoforms and found a large discrepancy between our predictions and perivascular NO measurements, suggesting the existence of nonenzymatic sources of NO. S- nitrosohemoglobin (SNOHb) has been suggested as a major source to release NO in the arteriolar lumen and induce hypoxic vasodilation. In the present study, we formulated a multicellular computational model to quantify NO exposure in arteriolar smooth muscle when the NO released by intraerythrocytic SNOHb is the sole NO source in the vasculature. Our calculations show an NO exposure of similar to 0.25-6 pM in the smooth muscle region. This amount does not account for the large discrepancy we encountered regarding perivascular NO levels. We also found that the amount of NO delivered by SNOHb to smooth muscle strongly depends on the SNOHb concentration and half- life, which further determine the rate of NO release, as well as on the membrane permeability of red blood cells (RBCs) to NO. In conclusion, our mathematical model predicts that picomolar amounts of NO can be delivered to the vascular smooth muscle by intraerythrocytic SNOHb; this amount of NO alone appears not sufficient to induce the hypoxic vasodilation.