Abstract: PO1410
High Dietary K+ Attenuates Salt-Induced NCC and mTORC1 Activity in Dahl Salt-Sensitive Rats
Session Information
- Fluid, Electrolyte, and Acid-Base Disorders: Basic
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
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