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Abstract: SA-PO316

Grain vs. Casein-Based Diet Differentially Impact Angiotensin II Hypertension (AngII-HTN) Responses in Female vs. Male Sprague Dawley Rats

Session Information

Category: Hypertension and CVD

  • 1403 Hypertension and CVD: Mechanisms

Authors

  • McFarlin, Brandon E., Keck School of Medicine of USC, Los Angeles, California, United States
  • Ralph, Donna, Keck School of Medicine of USC, Los Angeles, California, United States
  • Veiras, Luciana C., Cedar Sinai Medical Center, W. Hollywood, California, United States
  • McDonough, Alicia A., Keck School of Medicine of USC, Los Angeles, California, United States
Background

We previously reported that the baseline renal transporter profile in females (F) is distinct from that in males (M), specifically: lower PT NHE3 activity, NaPi2, claudin 2 and AQP1, and higher DT NCC, SPAK, claudin 7 and cleaved γENaC abundance in F vs. M. We reported that F and M rats respond differentially to AngII-HTN (400 ng/kg/min for 14 days) when fed casein-based diet (Envigo TD 88239, 0.74% NaCl, 2% KCl). In F, abundance of cortical NHE3, NHE3p, NKCC2, and NKCC2p were increased, and NCC, NCCp, and cleaved γENaC were unchanged, while in M, abundance of cortical NHE3, NHE3p, NKCC2, NKCC2p were unchanged and NCC, NCCp and cleaved γENaC were increased (Fig A). Additionally, AngII-HTN increased proteinuria in M but not F despite similar HTN (~150 mmHg).

Methods

We aimed to determine if differential responses to AngII-HTN ( as above) are also evident in SD rats fed grain based diet (LabDiet 5001), n=5 F and M.

Results

At baseline, in F fed casein (vs. grain) based diet, NHE3 and NHE3p are more abundant (1.27 ± 0.06 fold and 1.58 ± 0.15 fold) and NKCC2p and NCCp are less abundant (0.69 ± 0.04 and 0.7 ± 0.08), all p ≦ 0.01. M and F fed grain-based diet responded similarly to AngII-HTN (Fig B), with a pattern distinct from that in casein-fed rats: Cortical NHE3 decreased (M only), both M and F had significant decreases in abundance of medullary NHE3, NHE3p, NKCC2, NKA α1, and increases in cortical NKCC2, NKCC2p, NCC, NCCp and cleaved ENaC. Blood pressure and proteinuria were similarly increased in M and F on grain based diet.

Conclusion

In summary, diet impacts: 1) baseline Na transporter abundance, 2) Na transporters’ regulation during AngII-HTN, and 3) AngII-HTN provoked proteinuria. Responses to AngII-HTN are similar in grain-based diet fed F and M.

Funding

  • NIDDK Support