A Polyphenol-Rich Extract from Muscadine Grapes Prevents Hypertension-Induced Diastolic Dysfunction and Oxidative Stress

Abstract

Muscadine grapes are abundant in dietary polyphenols, but their effect on hypertension-induced cardiac damage is limited. This study assessed whether a muscadine grape skin/seed extract supplement (MGES) prevents hypertension-induced cardiac damage and oxidative stress. Male Sprague Dawley rats were treated for four weeks with drinking water, angiotensin II (Ang II) to induce hypertension, MGES, or both Ang II and MGES. Cardiac function assessed by echocardiography showed that Ang II increased systolic blood pressure while MGES alone or in combination with Ang II had no effect. Ang II increased E/e′, an indicator of left ventricular filling pressure and diastolic dysfunction, by 41% compared to Control and co-treatment with MGES prevented the Ang II-mediated increase, suggesting that the extract attenuated hypertension-induced diastolic function. Ang II infusion increased urinary 8-hydroxy-2′-deoxyguanosine and cardiac 4-hydroxynonenal and malondialdehyde, which were prevented by the extract. The antioxidant enzymes catalase and superoxide dismutase 1 activity and mRNA were increased significantly in animals treated with MGES alone or in combination with Ang II, suggesting that the extract upregulates oxidative stress defense mechanisms in cardiac tissue. Thus, MGES may serve as a medical food to protect the heart from hypertension-induced diastolic dysfunction caused in part by excessive reactive oxygen species production.

Active vitamin D corrects cerebrovascular dysfunction and aberrant vasopressin expression in the hypertension phenotype of 1α-hydroxylase knockout mice

“…Wiesmann et al reported that AngII-induced elevated systolic blood pressure results in impaired CBF and a decreased response to blood pressure lowering treatment in a mouse model for Alzheimer's disease [41][42]. As we known, endothelial dysfunction is associated with the oxidative stress in hypertension pathology [43][44][45][46]. Amounts of antioxidant scavengers, such as SOD, GPx, catalase and vitamin E, are decreased in patients with hypertension.…”

Concentrations of Transition Metal Ions in Rat Lungs after Tobacco Smoke Exposure and Treatment with His-Leu Dipeptide

“…Exposure to tobacco smoke was carried out for six weeks. Treatment with HL (administered by subcutaneous injection, analogously to angiotensin II administration in other studies [ 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 ]) started from the third week of exposure to tobacco smoke and lasted four weeks.…”

“…Administering 5 mg HL/kg body weight per day would result in the basal concentration (10 pM) in the whole rat body after about four hours following injection, assuming a 10 min half-life of HL because of the subcutaneous route (in contrast to intravenous injection) and the average rat tissue water content of 65.6% [ 88 ]. Although the chosen dosage may seem relatively low, angiotensin II is administered to rats usually subcutaneously in the concentration range of 0.1–1.5 mg/kg body weight per day, with biological effects observed on the level of the whole organism [ 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 ]. Therefore, our choice for dosage is higher than that of angiotensin II (calculating it, one should also consider the difference in molecular weights of these peptides, which means that we administered from 14- to 190-fold higher molar content of HL than angiotensin II administered in other studies).…”

“…Therefore, our choice for dosage is higher than that of angiotensin II (calculating it, one should also consider the difference in molecular weights of these peptides, which means that we administered from 14- to 190-fold higher molar content of HL than angiotensin II administered in other studies). However, we should note that we administered HL once per day, opposite to angiotensin II, which was usually administered constantly using an osmotic mini-pump [ 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 ].…”