Plasma Concentrations of Asymmetric Dimethylarginine, an Endogenous Nitric Oxide Synthetase Inhibitor, Are Elevated in Sickle Cell Patients but Do Not Increase during Painful Crises.

Abstract

Plasma concentrations of asymmetric dimethylarginine (ADMA), an endogenously produced inhibitor of nitric oxide (NO) synthase, are elevated and related to endothelial activation in clinically asymptomatic patients with sickle cell disease (SCD). However, ADMA concentrations have not been defined during acute vaso-occlusive complications. We determined plasma ADMA and arginine concentrations in 96 samples (40 collected in the clinically asymptomatic state and 56 collected at presentation with a painful crisis) of 44 HbSS patients (mean age 32±13 years, m:f=23:21) and in 39 samples (22 collected in the clinically asymptomatic state and 17 collected at presentation with a painful crisis) of 22 HbSC patients (mean age 30±14 years, m:f=10:12). Thirty-five race, sex and age matched HbAA blood donors served as healthy controls. Plasma ADMA concentrations were elevated in asymptomatic sickle cell patients as compared to healthy controls (HbSS: mean 0.7±0.1 umol/L, HbSC mean 0.5±0.1 umol/L, HbAA mean 0.4±0.1 umol/L; p<0.001 one way ANOVA). Plasma arginine concentrations were lower in asymptomatic HbSS patients as compared to asymptomatic HbSC patients and healthy controls (HbSS: mean 59.6±25.8 umol/L, HbSC mean 75.5±25.8 umol/L, HbAA mean 74.0±27.1 umol/L; p=0.03 one way ANOVA). Ratio's of ADMA to arginine (ADMA/Arginine × 1000) were highest in HbSS patients (HbSS: mean 16.2±11.6, HbSC mean 7.8±2.9, HbAA mean 6.3±3.2; p=0.001 one way ANOVA). In both HbSS and HbSC patients, neither ADMA (p=0.17/p=0.57), arginine (p=0.13/p=0.18) nor the ADMA/arginine ratio (p=0.88/p=0.08) differed between the asymptomatic phase and at presentation with a painful crisis. In conclusion, even though ADMA is elevated in SCD and therefore may well be involved in the development of chronic organ complications by limiting NO availability, ADMA concentrations are not affected during acute painful sickle cell crises.