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

Abstract

ObjectivesTo 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. MethodsEight-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 (AT1R) 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. ResultsConsumption 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 AT1R 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. ConclusionsOur 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 SourcesThis 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.