Endothelial dysfunction in patients with sickle cell disease is related toselective 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 n itric oxide (NO) plays a major role in the regulation of vasomotor tone in response to wall shear stress (WSS) variations and pharmacologic stimuli, H owever, little is known about endothelial NO production in patients with st eady-state SCD. We investigated endothelial NO production in response to fl ow or vasoactive agonists in 16 homozygous patients with steady-state SCD a nd 15 controls. Flow-mediated dilation (FMD), arterial diameter changes in response to 100% oxygen inhalation, blood viscosity, and calculated WSS wer e determined in all patients and controls. At baseline, WSS was higher in S CD patients than in controls, whereas arterial diameter was similar. In pat ients 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 ab olished. Using venous occlusion plethysmography, forearm blood flow (FBF) w as evaluated in response to acetylcholine, nitro-monomethyl-L-arginine (L-N MMA), and sodium nitroprusside (SNP) in subgroups of 9 controls and 7 patie nts 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 m L/min/100 mL in the controls, P < .001), whereas responses to L-NMMA and SN P were similar. These results suggest that endothelial dysfunction may prev ent the arterial diameter of patients with SCD from adapting to chronic or acute shear stress elevations. This may contribute to the pathophysiology o f vaso-occlusive crisis in patients with SCD. (Blood, 2001; 97:1584-1589) ( C) 2001 by The American Society of Hematology.