Background. Sodium overload is related to the development of primary hypertension and its complications.Methods. In 131 (65 female) treated hypertensives (average blood pressure 144/82 mmHg and duration of hypertension 11.7 years), we measured peripheral and central arterial pressures, peripheral (AIxP) and central (AIxC1, AIxC2) augmentation indices, pulse-wave velocity (PWV) and daily urinary sodium excretion, and conducted genetic studies ofACED/I andCYP11B2C-344T polymorphisms. Proximal (FELi) and distal (FDRNa) sodium reabsorption measurements were performed using endogenous lithium clearance.Results. We found statistically significant interactions between FELiandACED/I polymorphism with respect to AIxC2(PINT= 0.05) and between FELiandCYP11B2C-344T polymorphism with respect to AIxC1(PINT= 0.01), AIxC2(PINT= 0.04) and AIxP(PINT= 0.01). In the group ofACEI allele carriers compared with DD homozygotes, the AIxC1(154.1 vs 140.6%;p= 0.02), AIxC2(33.3 vs 26.9%;p= 0.02) and AIxP(94.6 vs 85.2%;p= 0.01) were higher in the subgroup with FELibelow the median value (FELi1), but not in the subgroup with FELiabove the median value (FELi2). In the group ofCYP11B2TT homozygotes compared with C allele carriers, we observed higher values of AIxC1(158.5 vs 146.4%;p= 0.03), AIxC2(36.0 vs 29.4%;p= 0.01) and AIxP(99.0 vs 88.7%;p= 0.005) in the FELi1 but not the FELi2 subgroup.Conclusions. In the population with assumed high dietary sodium intake and long-standing history of hypertension, the relation between proximal sodium reabsorption and the development of arterial stiffness depends on the genetic context of the selected genetic polymorphisms of the renin—angiotensin—aldosterone system, independent of blood pressure. [ABSTRACT FROM PUBLISHER]