Plasma levels of asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, are elevated in sickle cell disease
- 186 Downloads
In recent years an important role has been ascribed to a reduced nitric oxide (NO) availability in the pathophysiology of sickle cell disease (SCD). Endogenously produced inhibitors of NO synthase, in particular asymmetric dimethylarginine (ADMA), are currently considered of importance in various vascular disease states characterized by reduced NO availability. We determined ADMA levels in plasma of 12 adult sickle cell patients (eight HbSS and four HbSC), and compared these to plasma levels in race- and age-matched controls. Sickle cell patients were characterized by strongly elevated levels of ADMA [HbSS: median 0.63 μmol/l (interquartile range 0.54–0.85), HbSC: 0.43 μmol/l (0.40–0.46), HbAA: 0.33 μmol/l (0.32–0.35) p<0.001]. ADMA levels were highest in HbSS patients with lowest hemoglobin levels and highest leukocyte counts, and in HbSS patients ADMA levels were positively associated with serum levels of soluble vascular cell adhesion molecule-1. These results suggest an important role of ADMA in limiting NO availability in SCD, and its role in the pathophysiology of SCD should be further investigated.
KeywordsSickle cell disease Arginine Nitric oxide Asymmetric dimethylarginine (ADMA) Hemolysis Endothelium
- 12.Gladwin MT, Sachdev V, Jison ML, Shizukuda Y, Plehn JF, Minter K, Brown B, Coles WA, Nichols JS, Ernst I, Hunter LA, Blackwelder WC, Schechter AN, Rodgers GP, Castro O, Ognibene FP (2004) Pulmonary hypertension as a risk factor for death in patients with sickle cell disease. N Engl J Med 350:886–895CrossRefPubMedGoogle Scholar