Hypertension contributes to seven of the top ten leading causes of death in the US. About half of the hypertensive population is salt-sensitive, a condition defined by a sustained elevation of blood pressure after ingestion of dietary sodium. Among Black hypertensives, the percentage of salt-sensitivity rises to 70% representing a severe health disparity that is still poorly understood. There are few proposed mechanisms for salt-sensitive hypertension, but one promising hypothesis involves Peroxisome Proliferator Activated Receptor-alpha (PPAR-α), a nuclear protein originally identified in lipid metabolism. Our lab has demonstrated that PPAR-α knockout mice have higher mean arterial pressure than wild type (WT) mice after treatment with Angiotensin II (Ang II) (400 ng/kg/min). Our lab has also shown that, during Ang II infusion, mice treated with fenofibrate (a PPAR-α agonist) have attenuated MAP and elevated plasma interleukin-6 compared to WT. 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 via 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 cage 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). A second cohort for this experiment is currently underway with results pending. We hypothesize that all high salt groups will show higher SBP, and that C57 mice will show the lowest average SBP, lowest change in GFR, and highest PPAR-α expression. We hypothesize that B129 mice will have a higher SBP than C57 but lower than KO, and higher GFR than C57 but lower than KO. The results of our study will clarify the mechanism upon which PPAR-α acts upon renal function and may lead to future treatments for salt sensitive hypertension. This abstract was presented at the American Physiology Summit 2026 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.
Hatcher et al. (Fri,) studied this question.