528 The role of peroxisome proliferator-activated receptor-alpha on blood pressure, glomerular filtration rate, and renal inflammation during high-salt hypertension

Abstract

Objectives/Goals: The study’s goal is to investigate the role of PPAR-α on regulating blood pressure, glomerular filtration rate (GFR), renal inflammation, and renal sodium reabsorption in mice on a 4% high-salt diet. Methods/Study Population: GFR, systolic blood pressure (SBP), inflammatory biomarkers (KIM-1, TIMP2, NGAL, MCP-1, TNF-α, IL-6, IL-10, and IL-17), and renal sodium transporter expression (NKA, NHE3, NKCC2, NCC, ENaC, Aqp-2, and NHERF1) were measured in PPAR-α KO mice and wild-type controls treated with a 4% high-salt (HS) diet. Male C57BL6, B129S1, and PPAR-α KO mice (12 weeks old) will be treated with 4% HS diet for 28 days. Systolic blood pressure is measured by tail cuff. GFR is measured by transdermal FITC-Inulin radioactive fluorescence. Inflammatory biomarkers will be measured by cytokine array and western blot. Sodium transporter expression will be measured by western blot. Results/Anticipated Results: Baseline SBP was 146 ± 31 mmHg (C57), 140 ± 24 mmHg (B129), and 153 ± 23 mmHg (KO). After 21 days of normal (control diet) or treatment (HS diet), control systolic pressures were 139 ± 18 mmHg (C57), 107 ± 23 mmHg (B129) and 147 ± 34 mmHg (KO), while HS systolic pressures were 166 ± 23 mmHg (C57) and 119 ± 34 mmHg (B129). We are collecting blood pressure for the KO HS group. Baseline GFR was 1194 ± 140 µL/min/g (C57), 1167 ± 279 µL/min/g (B129), and 1191 ± 157 µL/min/g (KO). Discussion/Significance of Impact: We hypothesize significantly higher SBP, inflammatory marker expression, and renal sodium transporter expression in KO and B129 mice on a HS diet. We predict that PPAR-α expression in the kidney will be higher in C57 compared to B129. We predict that PPAR-α activity plays a vital role in reducing high-salt-induced hypertension and inflammatory markers.