Approximately 20-40% of adolescents have shown a reduction of urinary sodium excretion (U(Na)V) in response to blood pressure (BP) increase during behavioral stress. G protein-coupled receptor kinase 4 (GRK4) mediates the pressure and natriuresis relation. The present study investigated the impact of GRK4 genetic variants on U(Na)V under stress. A total of 664 normotensive adolescents including whites and blacks (17.6 +/- 3.3 yrs, 43.4% blacks) were recruited. Participants were subjected to a stress-protocol including three 10-min tasks (a social competence interview, a virtual reality car driving simulation test, and a video game challenge), concluded by a urine collection. Three functional polymorphisms including R65L, A142V and A486V were genotyped. Given blacks compared with whites had significantly higher systolic BP (SBP) levels during rest (p < 0.001) and stress (p <or= 0.001), there was no statistical difference in U(Na)V in response to stress between the two ethnic groups. In blacks, compared with R65R homozygotes, individuals with R65L or L65L genotype had significantly lower levels of stress-induced U(Na)V (8.42 +/- 0.63 versus 9.85 +/- 0.37 mEq/h, p = 0.01). In summary, BP elevation seems uncoupled with U(Na)V increase during behavioral stress in black adolescents. The 65L allele of the GRK4 gene is associated with stress-induced U(Na)V reduction, suggesting impaired sodium handling in affected black youth.