Active nitric oxide produced in the red cell under hypoxic conditions by deoxyhemoglobin-mediated nitrite reduction
Active nitric oxide produced in the red cell under hypoxic conditions by deoxyhemoglobin-mediated nitrite reduction
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DOI：
10.1074/jbc.m307572200
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发表时间：
2003-11-21
影响因子：
4.8
通讯作者：
Rifkind, JM
中科院分区：
文献类型：
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作者：
Nagababu, E;Ramasamy, S;Rifkind, JM
最近的研究引起了人们对红细胞在一氧化氮(NO)运输到微循环中的可能作用以及这种一氧化氮在促进血液通过微循环中的血管效应方面的极大兴趣。然而，人们对这种机制提出了许多问题。相反，我们确定了一种全新的机制来解释红细胞在将NO输送到微循环中的作用。这一新的机制导致了微循环中需要NO的地方产生NO。当氧分压降低时，NO与动脉血中的氧反应产生的亚硝酸盐在小动脉中被重新利用，形成的脱氧血红蛋白减少了亚硝酸盐的再生。亚硝酸盐被血红蛋白还原的结果是，生成的大部分NO保留在中间状态，其中NO与Hb(III)结合，并与Hb(II)结合的亚硝酸阳离子平衡。这个NO池与HB(II)NO不同，它是弱结合的，可以从血红素中释放出来。Hb(III)NO在氧气中的不稳定性及其在用Ar冲洗时的置换要求必须对新鲜裂解的样品进行可靠的红细胞NO测定，而不允许样品被氧化。新鲜血液标本中，Hb(III)NO占红细胞NO的75%，静脉血中的NO值明显高于动脉血。这些发现证实了亚硝酸盐在低氧压下的还原是红细胞一氧化氮的主要来源。这种一氧化氮的形成和从红细胞中的潜在释放可能在调节微循环中的血液流动方面产生重大影响。
Recent studies have generated a great deal of interest in a possible role for red blood cells in the transport of nitric oxide (NO) to the microcirculation and the vascular effect of this nitric oxide in facilitating the flow of blood through the microcirculation. Many questions have, however, been raised regarding such a mechanism. We have instead identified a completely new mechanism to explain the role of red cells in the delivery of NO to the microcirculation. This new mechanism results in the production of NO in the microcirculation where it is needed. Nitrite produced when NO reacts with oxygen in arterial blood is reutilized in the arterioles when the partial pressure of oxygen decreases and the deoxygenated hemoglobin formed reduces the nitrite regenerating NO. Nitrite reduction by hemoglobin results in a major fraction of the NO generated retained in the intermediate state where NO is bound to Hb(III) and in equilibrium with the nitrosonium cation bound to Hb(II). This pool of NO, unlike Hb(II) NO, is weakly bound and can be released from the heme. The instability of Hb(III) NO in oxygen and its displacement when flushed with argon requires that reliable determinations of red blood cell NO must be performed on freshly lysed samples without permitting the sample to be oxygenated. In fresh blood samples Hb(III) NO accounts for 75% of the red cell NO with appreciably higher values in venous blood than arterial blood. These findings confirm that nitrite reduction at reduced oxygen pressures is a major source for red cell NO. The formation and potential release from the red cell of this NO could have a major impact in regulating the flow of blood through the microcirculation.