Blood pressure, arterial stiffness and endogenous lithium clearance in relation to AGTR1 and AGTR2 gene polymorphisms

Introduction: Although recently a matter of epidemiologic controversy, sodium overload and its interaction with genetic factors predispose to hypertension and related target organ complications. Methods: In 131 (66 male) treated hypertensives, we measured peripheral and central arterial pressures and pulse wave augmentation indexes (AIx P , AIx C1 , AIx C2 ), pulse wave velocity (PWV), daily urinary sodium excretion and did genetic studies of AGTR1 A1166C and AGTR2 G1675A polymorphisms. Proximal (FE Li ) and distal (FDR Na ) sodium reabsorption measurements were performed using endogenous lithium clearance. Results: In men, we found interaction between FDR Na and AGTR2 G1675A polymorphism with respect to AIx C1 ( p INT =0.01), AIx C2 ( p INT =0.05) and AIx P ( p INT =0.006). Arterial stiffness increased with higher sodium reabsorption in the distal tubule, in the presence of AGTR2 G allele with the opposite tendency in A allele carriers. In the subgroup with FDR Na below median, as compared to those with FDR Na above median, the AIx C1 (139.6±3.8 vs 159.1±5.7%; p =0.009), AIx C2 (26.3±1.8 vs 33.3±1.7%; p =0.016) and AIx P (83.4±2.5 vs 96.5±2.6%; p <0.0001) were lower, in the G allele carrying men and GG homozygous women. Conclusions: The relation between sodium reabsorption in the distal tubule and the development of arterial stiffness depends on the AGTR2 G1675A polymorphism in blood pressure independent fashion.