Blood pressure, arterial stiffness and endogenous lithium clearance in relation to AGTR1 A1166C and AGTR2 G1675A 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.