Sickle cell disease and nitric oxide: a paradigm shift?
Traditionally the pathophysiology of sickle cell disease is thought to result from the polymerization of hemoglobin S in red cells, under hypoxic conditions, resulting in the occlusion of blood vessels. Adhesion of cells to the venular endothelium also appears to play a role. Recent studies have also suggested that in addition to the polymerization of hemoglobin S in the red blood cell, a deficiency of the endogenous vasodilator, nitric oxide may be involved. Hemoglobin released as a result of hemolysis rapidly consumes nitric oxide resulting in a whole program of events that inhibit blood flow. Therapies directed at decreasing the destruction of nitric oxide, increasing the production of nitric oxide, or amplifying the nitric oxide response may prove beneficial.
Mack
A Kyle
AK
Pediatric Oncology Branch, 10 Center Drive, MSC 1476, NCI, NIH, Bethesda, MD 20892-1476, United States. kmack@mail.nih.gov
Kato
Gregory J
GJ
D000755:Anemia, Sickle Cell / Q000378:metabolism / Q000503:physiopathology*; D006451:Hemoglobin, Sickle / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D006461:Hemolysis / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D009569:Nitric Oxide / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D006451:Hemoglobin, Sickle; D006454:Hemoglobins; D017382:Reactive Oxygen Species; D009569:Nitric Oxide