Endothelial dysfunction in patients with sickle cell disease is related to selective impairment of shear stress-mediated vasodilation.
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.
Service de Physiologie-Explorations Fonctionnelles and the Centre de la Drépanocytose, Hôpital Henri Mondor, APHP et Université Paris XII, France. laurent.belhassen@hmn.ap-hop-paris.fr
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Belhassen
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Pelle
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Sediame
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Bachir
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Carville
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Bucherer
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Lacombe
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Galacteros
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Adnot
D000109:Acetylcholine / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D016022:Case-Control Studies; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D010100:Oxygen / Q000008:administration & dosage / Q000494:pharmacology; D010991:Plethysmography; D012039:Regional Blood Flow; D013314:Stress, Mechanical; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D010100:Oxygen