Abstract P166: The Effect of a Muscadine Grape Extract on Angiotensin II-Induced Hypertension and Cardiac Damage

Abstract

Muscadine grapes, indigenous to the southeastern United States, are a dietary source of polyphenols, such as ellagic acid, quercetin, and resveratrol, which have both anti-inflammatory and antioxidant properties. Preclinical studies show that ground muscadine grape skins and seeds have anti-cancer effects, suggesting that supplementation with a muscadine grape extract (MGE) may serve as a chemotherapeutic or chemopreventive agent. As cancer patients often present with hypertension, diabetes, and other vascular pathologies, it is imperative to determine the effect of a muscadine grape supplement on these underlying comorbidities. The goal of this study was to determine whether MGE administered in the drinking water will exacerbate or improve hypertension and cardiac damage. Sprague-Dawley rats receiving a 4-week infusion of Ang II via subcutaneous osmotic mini-pump (24 μg/kg/h) had a significant increase in systolic blood pressure (123.1 ± 2.3 mm Hg in control vs. 213.1 ± 6.8 mm Hg in Ang II-treated; n=8; p < 0.0001). MGE supplementation had no effect on blood pressure or gross cardiac hypertrophy in either normotensive or hypertensive rats. Additionally, MGE did not alter stroke volume or cardiac output, measured by VEVO ultrasound. However, MGE ameliorated the Ang-II induced decrease in diastolic function, as measured by the E/E’ ratio (19.9 ± 0.8 in control, 28.1 ± 1.1 in Ang II-treated rats, 22.3 ± 2.0 in Ang II/MGE-treated rats; p < 0.05). Co-treatment with MGE also significantly reduced the Ang II-mediated increase in cardiomyocyte cross-sectional area (340.5 ± 12.0 μm 2 in control, 423.2 ± 17.1 μm 2 in Ang II-treated rats, and 342.6 ± 13.2 μm 2 in Ang II/MGE-treated rats, p < 0.01). MGE supplementation of Ang II-treated rats decreased interstitial cardiac fibrosis, measured by Picrosirius red staining (1.0 ± 0.1% in control, 2.0 ± 0.2% in Ang II-treated rats and 1.4 ± 0.1% in Ang II/MGE-treated rats, p < 0.05). These results demonstrate that treatment with MGE does not exacerbate hypertension or hypertension-induced cardiac damage but ameliorates cardiac hypertrophy, suggesting that MGE supplementation has an acceptable safety profile for use as an anti-cancer agent in hypertensive patients and may be used to treat cardiac hypertrophy and damage.