The Role of Peroxisome Proliferator Activated Receptor-alpha on Blood Pressure and Glomerular Filtration Rate during a High-Salt Diet

Hypertension is a major contributing factor to three of the top ten causes of death for Americans: heart disease, stroke, and kidney disease. Previous results from our laboratory demonstrate that Peroxisome Proliferator Activated Receptor-alpha (PPAR-α) knockout (KO) mice exhibit higher mean arterial pressure (MAP) during Angiotensin II (Ang II)-induced hypertension. We have also demonstrated that the PPAR-α agonist, fenofibrate, reduces MAP and plasma interleukin-6 (IL-6) during Ang II-treatment. Preliminary results from our laboratory also show that MAP and glomerular filtration rate (GFR) are reduced in IL-6 KO mice treated with Ang II. The goal of this study is to investigate the role of PPAR-α in regulating blood pressure and GFR in mice fed a 4% high salt (HS) diet. Systolic Blood Pressure (SBP), and GFR were measured in PPAR-α KO mice and wild-type controls fed a 4% HS diet. Twelve-week-old male C57BL6 (C57), B129S1 (B129), and PPAR-α knockout (KO) mice were fed with 4% HS diet for 8 weeks. Systolic blood pressure was measured by tail cuff. GFR was measured by transdermal FITC-Inulin radioactive fluorescence. Baseline SBP was 146 ± 31 mmHg (C57), 140 ± 24 mmHg (B129), and 153 ± 23 mmHg (KO). After 8 weeks of normal (control diet) systolic pressures were 139 ± 34 mmHg (C57), 128 ± 26 mmHg (B129) and 155 ± 27 mmHg (KO); while HS diet systolic pressures were 161 ± 19 mmHg (C57) and 125 ± 39 mmHg (B129) and 120 ± 20 PPAR-α 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). Mice fed a control diet for 8 weeks GFRs were 1063 ± 246 µL/min/g (C57), 908 ± 121 µL/min/g (B129), and 978 ± 75 µL/min/g (PPAR- α KO), GFRs of mice fed a HS diet were 781 ± 346 µL/min/g (C57), 1122 ± 80 µL/min/g (B129), and 876 µL/min/g (KO). After 8 weeks, metabolic results showed that control diet mice had an average body weight change from baseline of +5.0 g (C57), +2.0 g (B129), +2.5 g (KO), and daily urine production changes of -0.3 mL/day (C57), and no changes for B129 and PPAR-α KO control urine production. In the HS fed groups, metabolic results showed weight changes from baseline of +2.3 g (C57), +2.0 g (B129), with no change in PPAR-α KO body weight, and daily urine production changes of +3.0 mL/day (C57), +1.7 mL/day (B129), and +1.0 mL/day (PPAR-α KO). More mice are needed to determine if PPAR-α may provide therapeutic treatments in reducing high-salt-induced hypertension, inflammatory markers, and kidney disease. National Center For Advancing Translational Sciences of the National Institutes of Health (TL1TR001431) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.