Chen Kejing, Pittman Roland N, Popel Aleksander S
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Antioxid Redox Signal. 2007 Aug;9(8):1097-110. doi: 10.1089/ars.2007.1594.
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 approximately 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.
我们之前基于对不同一氧化氮（NO）合酶亚型的生化途径分析构建了计算模型，结果发现我们的预测与血管周围NO测量值之间存在很大差异，这表明存在非酶促来源的NO。有人提出S-亚硝基血红蛋白（SNOHb）是在小动脉管腔中释放NO并诱导缺氧性血管舒张的主要来源。在本研究中，我们构建了一个多细胞计算模型，以量化当红细胞内SNOHb释放的NO是脉管系统中唯一的NO来源时，小动脉平滑肌中的NO暴露量。我们的计算表明，平滑肌区域的NO暴露量约为0.25 - 6 pM。这个量并不能解释我们在血管周围NO水平方面遇到的巨大差异。我们还发现，SNOHb向平滑肌输送的NO量强烈依赖于SNOHb的浓度和半衰期，这进一步决定了NO的释放速率，以及红细胞（RBC）对NO的膜通透性。总之，我们的数学模型预测，红细胞内的SNOHb可将皮摩尔量的NO输送到血管平滑肌；仅靠这个量的NO似乎不足以诱导缺氧性血管舒张。
