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Abstract: PO1410

High Dietary K+ Attenuates Salt-Induced NCC and mTORC1 Activity in Dahl Salt-Sensitive Rats

Session Information

Category: Fluid, Electrolyte, and Acid-Base Disorders

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

Authors

  • Ferdaus, Mohammed Zubaerul, Pharmacology & Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts, United States
  • Moreira, Jesse D., Pharmacology & Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts, United States
  • Kim, Kiyoung, Pharmacology & Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts, United States
  • Puleo, Franco J., Pharmacology & Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts, United States
  • Wainford, Richard David, Pharmacology & Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts, United States
Background

Na+ reabsorption by renal Na+-Cl cotransporter (NCC) plays a key role in blood pressure (BP) regulation. Dahl Salt-Sensitive (DSS) rats exhibit aberrant NCC activity and salt-sensitive hypertension (HTN) when fed a high-salt diet. The renal mammalian target of rapamycin complex 1 (mTORC1) is also implicated in the pathogenesis of DSS HTN. Studies in normotensive mice suggested an inverse relationship between blood [K+] and NCC activity; however, the effect of dietary K+ on NCC activity in DSS rats is still controversial. Moreover, the impact of dietary K+ on mTORC1 activity is unknown.
Hypothesis: Dietary K+ supplement downregulates salt-induced NCC and mTORC1 activity in DSS rats.

Methods

3 month old male DSS rats were randomly placed on high salt (4% NaCl, HS, n=3) or HS + high K+ (5% K+, HS+HK, n=4) diet for 28 days. Another group of DSS rats, maintained on HS diet for 14 days, were placed on HS+HK for another 14 days (HS→HS+HK, n=4). NCC activity was assessed by Hydrochlorothiazide (HCTZ, NCC antagonist) injection (20 mg/kg, intraperitoneal) induced natriuretic response. Protein abundance was determined by western blotting. The ratio of phosphorylated ribosomal protein - S6Ser235/236 to total S6, was used as mTORC1 activity marker.

Results

In response to HCTZ, urinary Na+ excretion was trending lower in HS+HK and HS→HS+HK than HS group, while the baseline excretion was unaltered. Total NCC (tNCC) and phosphorylated NCC (pNCC) abundance, a surrogate for NCC activity, were trending lower in HS→HS+HK compared with HS group. Interestingly, mTORC1 activity was significantly reduced in HS→HS+HK.

Conclusion

Trending lower response in HS+HK and HS→HS+HK to HCTZ suggests that dietary K+ may counteract and reduce salt-induced NCC activation. Downregulation of mTORC1 reveals that dietary K+ can reverse salt-induced mTORC1 activation. Critically, our data suggest that compared with the initial phase, K+ is more effective in reducing salt-induced NCC and mTORC1 activity when added later to the diet, which may attenuate established HTN in DSS rats.

Funding

  • Other NIH Support