Department of Pathology and Center for Free Radical Biology, University of Alabama at Birmingham , Birmingham, Alabama.
Antioxid Redox Signal. 2013 Oct 10;19(11):1198-208. doi: 10.1089/ars.2012.4884. Epub 2013 Mar 4.
Recent studies have suggested that in addition to oxygen transport, red blood cells (RBC) are key regulators of vascular function by both inhibiting and promoting nitric oxide (NO)-mediated vasodilation. Most studies assume that RBC are homogenous, but, in fact, they comprise cells of differing morphology and biochemical composition which are dependent on their age, parameters that control NO reactions. We tested the hypothesis that distinct RBC populations will have differential effects on NO signaling.
Young and old RBC were separated by density gradient centrifugation. Consistent with previous reports, old RBC had decreased levels of surface N-acetyl neuraminic acid and increased oxygen binding affinities. Competition kinetic experiments showed that older RBCs scavenged NO∼2-fold faster compared with younger RBC, which translated to a more potent inhibition of both acetylcholine and NO-donor dependent vasodilation of isolated aortic rings. Moreover, nitrite oxidation kinetics was faster with older RBC compared with younger RBC; whereas no differences in nitrite-reduction kinetics were observed. This translated to increased inhibitory effect of older RBC to nitrite-dependent vasodilation under oxygenated and deoxygenated conditions. Finally, leukodepleted RBC storage also resulted in more dense RBC, which may contribute to the greater NO-inhibitory potential of stored RBC.
These results suggest that a key element in vascular NO-homeostasis mechanisms is the distribution of RBC ages across the physiological spectrum (0-120 days) and suggest a novel mechanism for inhibited NO bioavailability in diseases which are characterized by a shift to an older RBC phenotype.
Older RBC inhibit NO bioavailability by increasing NO- and nitrite scavenging.
最近的研究表明，除了氧气运输外，红细胞（RBC）通过抑制和促进一氧化氮（NO）介导的血管舒张，也是血管功能的关键调节因子。大多数研究假设 RBC 是同质的，但事实上，它们由形态和生化组成不同的细胞组成，这些细胞依赖于它们的年龄和控制 NO 反应的参数。我们测试了这样一个假设，即不同的 RBC 群体将对 NO 信号产生不同的影响。
通过密度梯度离心分离年轻和年老的 RBC。与之前的报道一致，衰老的 RBC 表面 N-乙酰神经氨酸水平降低，氧结合亲和力增加。竞争动力学实验表明，与年轻的 RBC 相比，衰老的 RBC 清除 NO 的速度快约 2 倍，这导致对乙酰胆碱和 NO 供体依赖性主动脉环血管舒张的抑制作用更强。此外，与年轻的 RBC 相比，衰老的 RBC 中硝酸盐氧化动力学更快；而硝酸盐还原动力学没有差异。这导致在含氧和脱氧条件下，衰老的 RBC 对硝酸盐依赖性血管舒张的抑制作用增加。最后，白细胞去除的 RBC 储存也会导致 RBC 更加密集，这可能是储存的 RBC 具有更大的 NO 抑制潜力的原因之一。
这些结果表明，血管中 NO 动态平衡机制的一个关键因素是 RBC 年龄在生理范围内（0-120 天）的分布，并且为以 RBC 表型向衰老转变为特征的疾病中 NO 生物利用度受抑制提供了一种新的机制。
衰老的 RBC 通过增加 NO 和亚硝酸盐的清除来抑制 NO 生物利用度。
