Lactate interferes with ATP release from red blood cells.
Lactate interferes with ATP release from red blood cells.
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乳酸会干扰红细胞释放 ATP。
DOI：
10.1152/ajpheart.01238.2006
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Ellsworth,MaryL
中科院分区：
文献类型：
--
作者：
Rozier,MichaelD;Zata,VincentJ;Ellsworth,MaryL
当暴露在低PO2环境中时，包括人类在内的大多数物种的红细胞都会释放更多的ATP，最终作为血管张力的调节器，使氧气供应与需求相匹配。在疟疾和脓毒症等病理情况下，存在血流分布不均，其严重程度往往与血清乳酸升高的程度相关，而不改变pH值。我们推测，乳酸水平的增加可能会削弱红细胞对低PO2条件做出适当反应的能力，从而阻止其重要的血流调节作用。使用体外系统和兔红细胞，我们评估了与乳酸孵育的细胞在急性暴露于低PO2时释放增加的ATP的能力。我们发现，在乳酸存在的情况下，红细胞不会释放三磷酸腺苷。然而，当加入临床上用来降低血乳酸水平的药物二氯乙酸钠时，ATP释放恢复到与对照细胞(无乳酸)没有区别的水平，即使细胞内的ATP水平没有变化。这些结果支持红细胞内存在一个可以独立调节的独特的ATP流动调节池，乳酸干扰了这个池中的ATP产生，从而减少了暴露在低PO2下可供释放的ATP的量。因此，如果乳酸水平能够降低，红细胞的血管调节能力应该会恢复，从而使氧气供应和氧气需求适当匹配。
Upon exposure to low Po2, the red blood cells of most species, including humans, release increased amounts of ATP that ultimately serves as a regulator of vascular tone matching oxygen supply with demand. In pathological conditions such as malaria and sepsis, a maldistribution of perfusion exists with its severity often correlated with the extent of elevation of serum lactate frequently in the absence of an alteration in pH. We hypothesized that the increased levels of lactate might impair the ability of red blood cells to appropriately respond to conditions of low Po2, thus preventing its important blood flow regulatory role. Using an in vitro system and rabbit red blood cells, we evaluated the capacity of cells incubated with lactate to release increased amounts of ATP in response to acute exposure to low Po2. We found that in the presence of lactate, the red blood cells did not release ATP. However, when sodium dichloroacetate, a drug used clinically to lower blood lactate levels, was added, ATP release was restored to levels that were not different from that of control cells (no lactate), even though intracellular levels of ATP were not. These results support the presence of a distinct flow regulatory pool of ATP within the red blood cell that can be independently regulated, and that lactate interferes with the ATP production within this pool, thereby diminishing the amount of ATP available for release on exposure to low Po2. Therefore, if lactate levels can be reduced, the vascular regulatory capacity of the red blood cell should be restored, thus enabling the appropriate matching of oxygen supply with oxygen demand.