Abstract 19713: Renal Mechanisms of Hypertension Induced by SNX5 Gene Silencing
We have reported that sorting nexin 5 (SNX5) plays an important role in the positive regulation of the renal dopamine receptor subtype 1 (D1R); siRNA-gene silencing of renal SNX5 increased the blood pressure (BP) of spontaneously hypertensive rats. In order to test the hypothesis that SNX5 gene silencing decreases renal sodium transport and increases blood pressure, we measured BP, water and sodium balance, and renal protein expression of sodium transporters in C57BL6/J mice treated with renal subcapsular infusion of SNX5- or mock- siRNA (one week). 8 male C57BL6 mice (1 year old) were uninephrectomized 3 weeks prior to the infusion of SNX5- or mock-siRNA (3 μg/kg/day, n=4/group). Urine was collected (24 hr) from mice in metabolic cages one day prior to the end of the siRNA infusion. SNX5-siRNA-treated mice, had elevated systolic (119±5.2, mm Hg, under anesthesia) and diastolic BPs (91.8±7.3), relative to mock-siRNA-treated mice (SBP=101.5±0.5, DBP=72±2.3). Food and water intake, body weight, urine volume/sodium excretion, and heart rate were similar in the two groups. Renal protein expressions (immunoblotting) of NHE3, NaPi2, NCC, β/γ-ENaC, and Na+K+ATPase were similar in the 2 groups. However, the renal protein expressions of NKCC2 (156±24, % of control) and α-ENaC (288±54%) were greater in SNX5-siRNA than mock-treated mice. These findings suggest that inhibition of SNX5 by siRNA increases sodium transporters in distal nephron segments. This may cause the impaired sodium excretion that may be responsible for the increased BP in SNX5-siRNA-treated mice.
Author Disclosures: X. Wang: None. L. Asico: None. H. Lin: None. P.A. Jose: None. V.M. Villar: None.
- © 2016 by American Heart Association, Inc.