Red cells taken from patients with mild sickle cell disease dilate blood vessels under low oxygen conditions, but to a lesser extent than normal red cells. In contrast, red cells from those with severe disease symptoms cause blood vessels to constrict when oxygen levels drop, they found, a response which would further exacerbate the oxygen deficiency. Treatment of red blood cells with nitric oxide reversed that effect, they reported.
"Our results suggest that abnormal blood vessel control by red blood cells contributes to the vessel obstruction characteristic of sickle cell disease, and that variation in symptom severity among patients may be explained, in part, by variable deficiency in the processing of nitric oxide," Stamler said.
In light of the discovery, the researchers call for a re-evaluation of the role that nitric oxide may play in other blood diseases and conditions characterized by a deficiency in oxygen delivery to tissues, such as heart failure, diabetes and pulmonary hypertension.
Collaborators on the study include lead author John Pawloski and Douglas Hess. The work was supported by the National Institutes of Health and a Doris Duke Clinical Scientist Development Award.