Female Dahl SS rats exhibit greater increases in blood pressure on a high-fat, high-salt diet than males

Abstract

Epidemiological data suggest that blood pressure (BP) in females is more sensitive to a high-fat (HF) diet than in males. To better understand the mechanisms driving greater increases in BP with HF in females, appropriate animal models are needed. Female Dahl rats have been shown to exhibit similar or greater increases in BP on a chronic HF diet compared to males. The goal of the current study was to test the hypothesis that HF loading will also exacerbate increases in BP in females vs. males when animals are placed on a HF/high-salt (HS) diet. To address this hypothesis, 6-wk-old male and female Dahl rats were implanted with telemetry devices to continuously measure mean arterial BP; n=4-7/group. Rats were allowed to recover for one week followed by one week of baseline BP recording. Rats were then placed on a HF diet (60% kcal from lard; Bio-Serv) for 2 weeks followed by a HF/HS diet (4% salt; Bio-Serv) for an additional 4 weeks. Controls were maintained on a normal-fat/normal-salt (NF/NS) diet throughout the study. Rats were weighed weekly and placed in metabolic cages at the end of the study to collect a 24-hr urine sample to measure protein and albumin excretion. Baseline BP values were comparable between males (119±2 mmHg) and females (122±3 mmHg). 2 wks of HFD alone increased BP in both sexes (males: 126±2 mmHg, females: 133±4 mmHg; Pdiet= 0.002, Psex=0.1, Pint=0.47). Switching rats to a HF/HS diet resulted in pronounced increases in BP, and females had a higher BP than males at the end of the study vs. HFD alone (156±6 vs. 173±10 mmHg; Pdiet<0.0001, Psex=0.024, Pint=0.2). Consistent with enhanced sensitivity of BP in females to HF/HS compared to males, protein excretion increased 78±3% when going from HF alone to HF/HS in females vs. 68±2% in males (p=0.040). Albumin excretion increased to comparable levels in both sexes when going from HFD to HF/HS (87±1 vs. 85±2 %; p=0.68). Importantly, HF/HS resulted in increased body weight in males but not females vs. control diet more (males: 370±9 vs. 398±7 g, females: 244±6 vs. 239±4 g), however, males weighed more than females (Pint=0.046, Pdiet=0.17, Psex<0.0001). Males on HF/HS also exhibited greater perirenal fat vs. control (17±1 vs. 13±2 g) with no differences in females (6±0.6 vs. 6±0.9 g; Pdiet=0.1368, Psex=<0.0001, Pint=0.1365). Neither sex nor diet impacted gonadal fat (males: 17±1 vs. 13±1 g; females: 18±4 vs. 20±1 g; Pdiet=0.4982, Psex=0.1106, Pint=0.1106). Total cholesterol was comparable between the sexes on HF/HS (2476±540 vs. 2216 ± 293 nM; p=0.65) and triglycerides were greater in males (0.46±0.06 vs. 0.22±0.02 mg/dL; p=0.012). In conclusion, HF increases BP sensitivity in female Dahl rats independently of overt increases in body weight or adiposity, establishing a model to study the mechanisms that cause females to lose their cardiovascular protection with HFD. Supported by 1U54HL169191. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.