Abstract: PO2140
Age-Dependent Regulation of the NCC and the Development of Salt-Sensitive Hypertension
Session Information
- Mechanisms of Kidney and Vascular Disease
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1403 Hypertension and CVD: Mechanisms
Authors
- Kim, Kiyoung, Boston University School of Medicine, Boston, Massachusetts, United States
- Puleo, Franco J., Boston University School of Medicine, Boston, Massachusetts, United States
- Frame, Alissa, 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 prevalence of hypertension (HTN) increases with age, and age-dependent HTN is associated with increased sympathetic tone and blood pressure (BP). Dietary sodium intake is a major risk factor for HTN as excessive dietary sodium intake leads to increases in BP in individuals that demonstrate the salt sensitivity of BP to evoke salt sensitive HTN (SSH). We have previously demonstrated excessive release of norepinephrine upregulates the activity of the renal sodium chloride cotransporter (NCC) to promote sodium reabsorption and salt sensitive hypertension. However, the regulation of the NCC with age remain unclear. Thus, we tested the hypotheses that 1) upregulation of NCC contributes to age-dependent HTN, and 2) aged rats develop SSH.
Methods
Three different age groups (3, 8, 16 month old (MO)) of male Sprague-Dawley (SD) rats were fed a normal salt (NS; 0.6% NaCl) or HS (4% NaCl) diet for 21 days respectively. On day 21, basal MAP and NCC activity (peak natriuresis to IV hydrochlorothiazide (2mg/kg) infusion) were measured in vivo. The expression of total NCC, phosphorylated NCC, with-no-lysine [K] kinases (WNK) 1, WNK4, STE20/SPS1-related proline-alanine-rich protein kinase (SPAK), oxidative stress responsive kinase 1 (OxSR1), and phosphorylated SPAK/OxSR1 were assessed via immunoblotting (N=6/gp).
Results
Male SD rats develop age-dependent HTN with increased NCC activity and expression, and increased WNK1 expression. Aged male SD rats developed SSH, impaired dietary salt evoked suppression of NCC activity, phosphorylation, and the expression of kinases SPAK and OxSR1.
Conclusion
These data suggest that the NCC contributes to the development of age-dependent HTN. Moreover, dysregulation of the NCC may play a pivotal role in the development of age-dependent SSH.
MO, month old; NS, 0.6% NaCl; HS, 4% NaCl. *p<0.05 vs. respective NS group; #p<0.05 vs. respective 3 MO group; † p<0.05 vs. respective 8 MO group.