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Abstract: PO1816

Sex-Dependent Regulation of the WNK-NCC Pathway via Ubiquitination in Response to Dietary High Salt Intake in Young Sprague-Dawley Rats

Session Information

Category: Hypertension and CVD

  • 1403 Hypertension and CVD: Mechanisms

Authors

  • Kim, Kiyoung, Boston University School of Medicine, Boston, Massachusetts, United States
  • Ferdaus, Mohammed Zubaerul, Boston University School of Medicine, Boston, Massachusetts, United States
  • Wainford, Richard David, Boston University School of Medicine, Boston, Massachusetts, United States
Background

The thiazide-sensitive Na+-Cl cotransporter (NCC), located in the apical membrane of distal convoluted tubule, fine-tunes sodium reabsorption and regulates blood pressure. The NCC is downregulated by high salt intake in normotensive salt resistant rats. These studies investigated the potential mechanistic pathways by which NCC is degraded in response to high salt intake in male and female Sprague-Dawley (SD) rats.

Methods

3-month-old normotensive male and female SD rats were fed a normal salt (NS; 0.6% NaCl) or HS (4% NaCl) diet for 21 days. On day 21, the kidneys were collected and ~200 mg of the renal cortex was used to measure the expression of total NCC, WNK1, WNK4, Nedd4-2, Sortilin, KLHL3, and calcineurin via immunoblotting (N=5~6/group).

Results

A 21-day HS diet evokes the suppression of total NCC protein expression in young normotensive male and female SD rats. A HS diet downregulated WNK1 in male but not female SD rats. A HS diet suppressed the expression of the full-length and short WNK4 variants in female SD rats only. There was a trend for HS to increase Nedd4-2 expression in male SD rats (P=0.06), in contrast female rats downregulated Nedd4-2 in response to HS. The expression of sortilin, KLHL3, and calcineurin was suppressed by a HS diet in female rats only.

Conclusion

These data suggest that in response to a HS diet young female SD rats exhibit greater ubiquitin-dependent proteolytic and lysosomal degradation of the NCC than young male SD rats to regulate sodium homeostasis and blood pressure via a WNK-dependent signaling pathway.

Table 1: NS, 0.6% NaCl; HS, 4% NaCl. *P<0.05 vs. respective NS Group.