NITRIC OXIDE BINDING TO CROSS-LINKED HUMAN FERRIHEMOGLOBINS

血管内给予无基质血红蛋白似乎是 与肺和全身血压的升高密切相关。 这种高血压反应归因于以下因素的相互作用： 血红蛋白和内皮源性舒张因子（EDRF），现在是 据信是一氧化氮（NO）。 我们探索了 NO和氧化的人血红蛋白之间的关系， 未修饰的HbAo与两种化学交联的血红蛋白的HbAo。 的 后者是有前途的血液替代品候选人，由于他们的低氧 四聚体结构的亲和力和更大的稳定性。 修改后的 检查的形式是HbA=-DBBF，在α链之间交联， 双（3，5-二溴水杨基）富马酸酯和HbA-FMDA，在β- 链与富马酰基单-二溴阿司匹林。 NO结合的双相动力学 的铁血红素，观察到，由于不同的反应性 α链和β链。 两个阶段的速率在 修饰的血红蛋白，表明二聚体间交联的变化， α链和β链血红素口袋。 在一个缓慢的后续 过程中，（FeIII-NO）络合物的铁血红素被还原，如图所示。 （FeII-NO）光谱的出现。 减少发生在不同的 研究的血红蛋白的速率，最快的时间过程显示， 修改的形式。 如果细胞外基质的血管收缩作用 血红蛋白包括在氧化和还原形式之间循环， 暴露于NO时，观察到的改性的 血红蛋白可能被证明具有生理学意义。

Intravascular administration of stroma-free hemoglobin appears to be strongly correlated with a rise in pulmonary and systemic blood pressure. This hypertensive response has been attributed to interactions between hemoglobin and the endothelium-derived relaxing factor (EDRF), which is now believed to be nitric oxide (NO). We have explored the interactions between NO and oxidized human hemoglobin, comparing the behavior of unmodified HbAo with that of two chemically cross-linked hemoglobins. The latter are promising blood substitute candidates due to their lower oxygen affinity and greater stability of tetrameric structures. The modified forms examined were HbA=-DBBF, cross-linked between the alpha chains with bis (3,5-dibromosalicyl) fumarate, and HbA-FMDA, modified between the beta chains with fumaryl mono-dibromoaspirin. Biphasic kinetics of NO binding to the ferric hemes were observed, attributable to differing reactivities of alpha and beta chains. The rates of the two phases were altered in the modified hemoglobins, indicating that interdimeric cross-linking changes both alpha and beta chain heme pockets. In a much slower subsequent process, the ferric hemes of (FeIII-NO) complex became reduced, as shown by appearance of the (FeII-NO) spectrum. The reduction occurred at differing rates for the hemoglobins studied, with the fastest time courses shown by the modified forms. If the vasoconstrictive effects of extracellular hemoglobin involve cycling between oxidized an reduced forms in response to exposure to NO, the differences in rate constants observed for the modified hemoglobins may prove to be of physiological significance.