Abstract 026: Sex Specific Regulation Of The Sodium-chloride Cotransporter And The Salt Sensitivity Of Blood Pressure In Age-dependent Hypertension

Abstract

Objectives: Blood pressure (BP) increases with age in a sex-dependent manner and a high salt diet (HSD) raises BP in salt sensitive individuals. The Na + -Cl - cotransporter (NCC) in renal cortex contributes to the fine-tuning of sodium reabsorption and BP regulation. We hypothesized that 1) increased NCC activity and expression contributes to sex- and age-dependent hypertension (HTN), and 2) age impairs HSD evoked suppression of NCC activity and expression with age to drives the development of salt sensitive hypertension (SSH). Methods: Three different age groups (3, 8, 16 month old) of male and female Sprague-Dawley (SD) rats were fed a normal salt diet (NSD; 0.6% NaCl) or HSD (4% NaCl) for 21 days. On day 21, basal MAP and NCC activity (peak natriuresis to IV hydrochlorothiazide (2mg/kg) infusion) were measured in vivo. The expression of 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 their phosphorylation status was assessed via immunoblotting (N=6/gp) Results: Male, but not female, rats develop age-dependent HTN with increased NCC activity and increased expression of NCC, WNK1, SPAK and phosphorylated SPAK/OxSR1 with age during NSD. A HSD evokes SSH with age in male, but not female, rats, and HSD evoked suppression of NCC activity and expression, WNK1, SPAK, OxSR1 and their phosphorylation is impaired in aged male rats. Conclusion: These findings suggest that 1) increased NCC activity and expression contributes to age-dependent HTN in male, but not female, SD rats, and 2) HSD evoked suppression of NCC is impaired with age driving SSH in male but not female SD rats.