Low concentrations of nitric oxide increase oxygen affinity of sickle erythrocytes in vitro and in vivo
Low concentrations of nitric oxide increase oxygen affinity of sickle erythrocytes in vitro and in vivo
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DOI：
10.1172/jci119631
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发表时间：
1997-09-01
影响因子：
15.9
通讯作者：
Zapol, WM
中科院分区：
文献类型：
--
作者：
Head, CA;Brugnara, C;Zapol, WM
镰状细胞病(SCD)的特征是脱氧镰状血红蛋白(HBS)的聚合。在SCD患者中，减少红细胞(RBC)镰刀样改变的一个策略是增加HBS的氧亲和力。我们的目的是确定低浓度的一氧化氮(NO)气体是否会增加含有纯合子HBs(SS)的红细胞的氧亲和力，将含有正常成人血红蛋白(AA)或SS的红细胞体外培养在不同浓度的NO(高达80ppm)中，并测量氧解离曲线(ODCs)。另外，3名AA志愿者和9名SS志愿者在空气中呼吸80ppm NO 45min前后取血，并测定其ODC值。SS红细胞在体外暴露于80ppm NO 5分钟或更长时间，使血红蛋白50%氧饱和时的氧分压(P-50)平均降低15%(4.8ppm/-1.7mmHg平均值+/-SE；铂0.001)。SS-RBC氧亲和力增加与NO浓度呈正相关。AA红细胞的P-50不变(P>；0.1)。在SS志愿者中，呼吸80ppm NO 45min，P-50下降(P<；0.001)4.6+/-2.0毫米汞。在停止呼吸60分钟后，7名志愿者中有5名的RBC P-50持续下降。AA受试者呼吸NO后RBC P-50无明显变化(P>；0.1)。所有呼吸NO的受试者高铁血红蛋白(MHb)均维持在较低水平(SS MHb 1.4+/-0.5%)，P-50降低与MHb变化无相关性(r=0.02)。因此，低浓度的NO在体外和体内增强了镰状红细胞的氧亲和力，而没有显著的MHb产生。这些结果表明，低浓度的NO气体可能为SCD的治疗提供了一种有吸引力的新的治疗模式。
The hallmark of sickle cell disease (SCD) is the polymerization of deoxygenated sickle hemoglobin (HbS). In SCD patients, one strategy to reduce red blood cell (RBC) sickling is to increase HbS oxygen affinity. Our objective was to determine if low concentrations of nitric oxide (NO) gas would augment the oxygen affinity of RBCs containing homozygous HbS (SS), Blood containing normal adult hemoglobin (AA) or SS RBCs was incubated in vitro in the presence of varying concentrations of NO up to 80 ppm, and oxygen dissociation curves (ODCs) were measured. In addition, blood was obtained from three AA and nine SS volunteers, before and after breathing 80 ppm NO in air for 45 min, and the ODCs were measured. Exposure of SS RBCs to 80 ppm NO in vitro for 5 min or longer decreased the partial pressure of oxygen at which hemoglobin is 50% saturated with oxygen (P-50), an average of 15% (4.8+/-1.7 mmHg mean+/-SE; Pt 0.001). The increase in SS RBC oxygen affinity correlated with the NO concentration. The P-50 of AA RBCs was unchanged (P > 0.1) by 80 ppm NO. In SS volunteers breathing 80 ppm NO for 45 min, the P-50 decreased (P < 0.001) by 4.6+/-2.0 mmHg. 60 min after NO breathing was discontinued, the RBC P-50 remained decreased in five of seven volunteers in whom the ODC was measured. There was no RBC P-50 change (P > 0.1) in AA volunteers breathing NO. Methemoglobin (Mhb) remained low in all subjects breathing NO (SS Mhb 1.4+/-0.5%), and there was no correlation (r = 0.02) between the reduction in P-50 and the change in Mhb. Thus, low concentrations of NO augment the oxygen affinity of sickle erythrocytes in vitro and in vivo without significant Mhb production. These results suggest that low concentrations of NO gas may offer an attractive new therapeutic model for the treatment of SCD.