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Abstract: PO1080

Cholesterol Efflux on Sodium-Sensitive Blood Pressure

Session Information

Category: Fluid, Electrolyte, and Acid-Base Disorders

  • 901 Fluid, Electrolyte, and Acid-Base Disorders: Basic

Authors

  • Oliveira, Karin Carneiro de, Stony Brook University Renaissance School of Medicine, Stony Brook, New York, United States
  • Repetti, Robert Lawrence, Stony Brook University Renaissance School of Medicine, Stony Brook, New York, United States
  • Rohatgi, Rajeev, Northport VA Medical Center, Northport, New York, United States
Background

Na sensitive BP is linked to greater mortality than Na resistant hypertension. Dyslipidemia and changes in plasma membrane (PM) lipid composition contribute to Na sensitivity. In addition, diets enriched in cholesterol (chol) (1) raise cortical collecting duct (CCD) chol, (2) stimulate ENaC, and (3) repress natriuretic factors. Renal ABCA1, a chol efflux protein, increases in chol fed mice to mitigate cellular chol integration. Therefore, we hypothesize renal tubular ABCA1 ablation will lead to Na dependent changes in BP.

Methods

Transgenic mice (TgPAX8rtTA;tetO-Cre/+), which express CRE recombinase in tubular epithelia when fed doxycycline (dox), were bred with mice expressing floxed ABCA1 to generate a model deficient in tubular ABCA1 (FF). Tail cuff systolic BP (SBP; Visitech) and urine volume after diuretic administration was measured in mice. Immunoblotting was performed on kidney protein lysate.

Results

Immunoblotting of renal PM showed reduced ABCA1 (50±11%; n=6, p<0.05) in FF compared to littermate wildtypes (WTs; 100±7% (n=5)) mice. The SBP of FF (n=11) mice was greater immediately post-dox and during chol or high Na feeding (Fig.1; #, p<0.05 vs WT) compared to WTs (n=15). Low Na diet abolished SBP differences between mice, while 6 weeks (W) of 1% chol diet raised the SBP in ABCA1 FF vs FF mice post-dox feeding (Fig. 1; *, p<0.05 vs. FF post-dox). No difference NKCC2, NCC or α-ENaC protein abundance was noted in whole kidney lysate; however, γ-ENaC 83 kD and cleaved 70 kD subunits were increased in FF compared to WT kidney. Furosemide injection induced a greater diuretic effect in FF (n=4; 1.35±0.08 mL) vs WT (n=4; 0.88±0.08 mL; p<0.05).

Conclusion

Tubular ABCA1 deficiency stimulates Na dependent SBP which we speculate is related to enhanced Na dependent ENaC and NKCC2 activity.

SBP of FF and WT mice in days (D) and weeks (W) of diet

Funding

  • Veterans Affairs Support