Hypertension is a prevalent and significant contributor to morbidity and mortality from heart failure. It is estimated that 50% of patients with hypertension are salt-sensitive;their blood pressure is elevated by higher sodium intake and reduced by lower sodium intake. The DASH (Dietary Approaches to Stop Hypertension) clinical trials provided evidence that diets rich in fruits and vegetables significantly reduced blood pressure. One recent study attempted to nutritionally model the DASH diet to assess affects on hypertension in rats. Despite a detailed modeling of the nutrient profile of the DASH diet, the study failed to detect an affect on blood pressure. Therefore, a whole foods model containing non-nutritive phytochemicals may be required to assess the depressor effect of the DASH diet, versus elevated nutrients alone. Preliminary studies tested the hypothesis that a grape-enriched diet would impact experimental heart failure in the Dahl Salt-Sensitive rat model of hypertension-associated heart failure. The diet incorporation of freeze-dried whole grape powder significantly lowered blood pressure, cardiac hypertrophy, cardiac fibrosis, and cardiac oxidative damage. In addition, grape-fed rats displayed improved cardiac function and endogenous antioxidant glutathione reserve. However, the mechanisms of these effects remain unknown. Grape diets may have reduced pathogenesis indirectly by lowering oxidative stress-mediated redox AP-1 and NF-kB signaling, which in turn regulates the expression of pro-fibrotic and pro-inflammatory cytokines. Grape diets may have also acted directly by enhancing endogenous antioxidant defense. Bioavailable polyphenols can activate transcription factors Nrf2 and AhR to activate xenobiotic response elements(XRE) and antioxidant response elements(AREs) in the genome, which activates the expression of genes related to antioxidant defense like glutathione. The two pronged, central hypothesis is that in Dahl-SS rats, 1) grape-enriched diets are associated with decreased activation of cardiac NF-KB and AP-1 and their transcripts related to inflammation and fibrosis (AIM 1), and increased activation of cardiac AhR and Nrf2 and the expression of antioxidant defense genes(AIM 2), and 2) the effects of grape diet on cardiac AhR and Nrf2 is sustained even in healthy Dahl-SS hearts. The proposed studies are innovative because they go beyond transient effects of diet and examine the accumulated, cardiac-specific effects of a polyphenol-enriched diet on both healthy and diseased hearts. The study is significant for public health because findings could improve knowledge of the value of dietary approaches for both prevention or management of hypertension and associated cardiac pathology.
| Seymour, E Mitchell; Bennink, Maurice R; Bolling, Steven F (2013) Diet-relevant phytochemical intake affects the cardiac AhR and nrf2 transcriptome and reduces heart failure in hypertensive rats. J Nutr Biochem 24:1580-6 |
| Seymour, E Mitchell; Bennink, Maurice R; Watts, Stephanie W et al. (2010) Whole grape intake impacts cardiac peroxisome proliferator-activated receptor and nuclear factor kappaB activity and cytokine expression in rats with diastolic dysfunction. Hypertension 55:1179-85 |
| Seymour, E M; Singer, Andrew A M; Bennink, Maurice R et al. (2008) Chronic intake of a phytochemical-enriched diet reduces cardiac fibrosis and diastolic dysfunction caused by prolonged salt-sensitive hypertension. J Gerontol A Biol Sci Med Sci 63:1034-42 |
