Endothelial dysfunction in patients with sickle cell disease is related to selective impairment of shear stress-mediated vasodilation
Endothelial dysfunction in patients with sickle cell disease is related to selective impairment of shear stress-mediated vasodilation
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DOI：
10.1182/blood.v97.6.1584
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发表时间：
2001-03-15
期刊：
影响因子：
20.3
通讯作者：
Adnot, S
中科院分区：
文献类型：
--
作者：
Belhassen, L;Pelle, G;Adnot, S
内皮细胞和红细胞之间的相互作用可能导致镰状细胞病（SCD）的血管并发症。内皮源性一氧化氮（endothelial-derived nitric oxide，NO）在血管紧张性反应中起重要作用。然而，对于稳态SCD患者内皮NO的产生知之甚少。我们研究了16例稳定状态SCD纯合子患者和15例对照者对血流或血管活性激动剂的内皮NO产生反应。测定所有患者和对照组的血流介导性扩张（FMD）、对100%吸氧反应的动脉直径变化、血液粘度和计算的WSS。在基线时，SCD患者的WSS高于对照组，而动脉直径相似。在SCD患者中，FMD受损（1.73% +/- 0.44% vs对照组3.97% +/- 0.24%，P <0.001），对100%氧气的血管收缩反应消失。使用静脉闭塞体积描记法，在9名对照组和7名SCD患者的亚组中评价前臂血流（FBF）对乙酰胆碱、硝基单甲基-L-精氨酸（L-NMMA）和硝普钠（SNP）的反应，乙酰胆碱诱导患者FBF显著增加（9.7 +/- 2.9 mL/min/100 mL前臂体积vs 2.5 +/- 1.5 mL/min/100 mL对照组，P <0.001），而对L-NMMA和SNP的反应相似。这些结果表明，内皮功能障碍可能会阻止SCD患者的动脉直径适应慢性或急性剪切应力升高。这可能有助于SCD患者血管闭塞危象的病理生理学。（血液，2001; 97：1584-1589）（C）2001年由美国血液学会。
Interactions between the endothelium and erythrocytes may contribute to the vascular complications of sickle cell disease (SCD). Endothelium-derived nitric oxide (NO) plays a major role in the regulation of vasomotor tone in response to wall shear stress (WSS) variations and pharmacologic stimuli, However, little is known about endothelial NO production in patients with steady-state SCD. We investigated endothelial NO production in response to flow or vasoactive agonists in 16 homozygous patients with steady-state SCD and 15 controls. Flow-mediated dilation (FMD), arterial diameter changes in response to 100% oxygen inhalation, blood viscosity, and calculated WSS were determined in all patients and controls. At baseline, WSS was higher in SCD patients than in controls, whereas arterial diameter was similar. In patients with SCD, FMD was impaired (1.73% +/- 0.44% vs 3.97% +/- 0.24% in the controls, P < .001) and vasoconstriction in response to 100% oxygen was abolished. Using venous occlusion plethysmography, forearm blood flow (FBF) was evaluated in response to acetylcholine, nitro-monomethyl-L-arginine (L-NMMA), and sodium nitroprusside (SNP) in subgroups of 9 controls and 7 patients with SCD, Acetylcholine induced a significantly greater FBF increase in the patients (9.7 +/- 2.9 mL/min/100 mL of forearm volume vs 2.5 +/- 1.5 mL/min/100 mL in the controls, P < .001), whereas responses to L-NMMA and SNP were similar. These results suggest that endothelial dysfunction may prevent the arterial diameter of patients with SCD from adapting to chronic or acute shear stress elevations. This may contribute to the pathophysiology of vaso-occlusive crisis in patients with SCD. (Blood, 2001; 97:1584-1589) (C) 2001 by The American Society of Hematology.