Raspberry Consumption Reduces ACE1 and NADPH Oxidase Expression in the Kidneys of Mice, Mitigating the Hypertensive Effects of a High-Fat, High-Sucrose Diet.

OBJECTIVES: To determine whether a diet supplemented with raspberry (RB) is effective at reducing high-fat, high-sucrose (HFHS) diet-induced hypertension through alterations in the renin angiotensin system (RAS) in the kidneys. METHODS: Eight-week-old male C57BL/6 mice were fed an AIN-93M control diet with or without 10% w/w freeze-dried RB for 4 weeks. They were then randomized into three groups: control (CON), HFHS, or RB + HFHS for 24 weeks. Blood pressure (BP) was measured via tail-cuff plethysmography (n = 6–9/group). Mice were then sacrificed and kidneys were collected for analysis (n = 4–6/group). Protein expression of the pro-oxidant enzymes, NADPH oxidase (NOX) 1 and 4, and RAS components, angiotensin II receptor type 1 (AT(1)R) and angiotensin converting enzyme 1 (ACE1), were assessed by western blot. Data were analyzed by ANOVA or Kruskal-Wallis, dependent on normality, followed by Dunnett's post-hoc analysis for multiple comparisons. RESULTS: Consumption of a HFHS diet for 24 weeks led to a significant increase in systolic BP (120.6 ± 6.8 vs. 98.0 ± 7.1 mmHg, p < 0.0001) compared to CON, which was prevented by dietary RB supplementation (98.9 ± 6.3 mmHg, P < 0.0001). In the kidney, a HFHS diet significantly increased the expression of NOX1 (2.20 ± 0.61 vs. 1.00 ± 0.32-fold, p = 0.008) and NOX4 (2.10 ± 0.86 vs. 1.00 ± 0.32-fold, p = 0.01) compared to CON. RB consumption attenuated the expression of NOX1 (1.22 ± 0.69-fold, p = 0.03) and NOX4 (0.72 ± 0.16-fold, p = 0.005) compared to the HFHS. Expression of AT1R in the kidney was significantly increased by HFHS diet consumption (3.19 ± 1.7 vs. 1.00 ± 0.54-fold, p = 0.02) compared to CON. While RB consumption did not significantly decrease AT(1)R compared to the HFHS group (1.90 ± 0.38-fold, p = 0.1), its expression did not differ significantly from control (p = 0.3). RB consumption did, however, significantly decrease expression of ACE1 in the kidney (0.96 ± 0.25 vs. 0.29 ± 0.16-fold, p = 0.0009) compared to HFHS. CONCLUSIONS: Our results suggest the potential for RB to mitigate the hypertensive effects of a HFHS diet by favorably altering the expression of RAS components and markers of oxidative stress in the kidney. FUNDING SOURCES: This work is supported by the Lewis College Foundation and the Agriculture and Food Research Initiative (grant no. 2019–67,017-29,257/project accession no. 1,018,642) from the USDA National Institute of Food and Agriculture.