Effect of a Resveratrol/Quercetin Mixture on the Reversion of Hypertension Induced by a Short-Term Exposure to High Sucrose Levels Near Weaning and a Long-Term Exposure That Leads to Metabolic Syndrome in Rats

Abstract

Hypertension is an important global public health problem. Excess sucrose during a short period near weaning (short sucrose period, SSP; sucrose during rat postnatal days 12 to 28) increases the risk of developing hypertension during adulthood and sucrose ingestion for 6 months after weaning also results in metabolic syndrome (MS) accompanied by hypertension. The aim of this study was to test if the mechanisms that lead to hypertension induced by SSP and MS are similarly modified by a resveratrol/quercetin mixture (RSV/QSC) that targets epigenetic cues. We studied the reversion of hypertension by an RSV/QSC mixture administered for 1 month (from month 6 to month 7 of age) in these two models, since it is effective against some signs of MS. RSV/QSC might determine Sirtuin 1 (SIRT1) and Sirtuin 3 (SIRT3) expression that modulates the expression of endothelial nitric oxide synthase (eNOS), which synthesizes nitric oxide (NO), and of superoxide dismutases (SOD1 and 2), which are antioxidant enzymes that have an impact on the NO levels. Short- (SSP) and long-term (MS) exposure to sucrose induced hypertension and RSV/QSC reversed it. It increased the insulin sensitivity, which may determine the eNOS expression. eNOS expression was decreased in aortas from SSP and MS rats and RSV/QSC only elevated its levels in aortas from MS rats. SIRT1 was also only increased in the MS aortas. Hypertension was accompanied by a decrease in total non-enzymatic antioxidant defenses in SSP and MS aortas, which improved with the RSV/QSC treatment. SOD1 expression was not modified by the sucrose treatments, but SOD2 expression was decreased in SSP and MS aortas. The RSV/QSC treatment increased SOD1 expression in MS aortas. SIRT3 was not modified by the sucrose or RSV/QSC treatments. In conclusion, SSP and MS lead to hypertension, but MS leads to more possible epigenetically- regulated mechanisms related to high blood pressure that could be targeted by the RSV/QSC mixture. Therefore, treatment has better effects on hypertension produced by MS.

Resveratrol in the Hypothalamic Paraventricular Nucleus Attenuates Hypertension by Regulation of ROS and Neurotransmitters

“…The authors of [ 43 ] found evidence that resveratrol, an anti-inflammatory and antioxidant substance, is an effective activator of SIRT1 [ 10 ]. In addition, SIRT1 overexpression in the rostral ventrolateral medulla (RVLM), another central region that regulates sympathetic activity, led to lower blood pressure and reduced sympathetic outflow by lowering ROS levels in spontaneously hypertensive rats [ 44 , 45 ].…”

Progress in the Preclinical and Clinical Study of Resveratrol for Vascular Metabolic Disease

“…Thus, more clinical trials need to be conducted to clarify the effects of RSV on blood pressure. Novel methods used to enhance the efficacy of RSV in treating hypertension, such as combining RSV with other compounds [ 92 ] and using nanocarriers [ 93 ], are also worthy to be further developed.…”

Oxidative, Reductive, and Nitrosative Stress Effects on Epigenetics and on Posttranslational Modification of Enzymes in Cardiometabolic Diseases

“…An elevated sucrose ingestion which leads to OS has been associated to the development of hypertension. We have previously published that the administration of sucrose during a short period near weaning in rats (postnatal days 12 to 28) increases the risk of developing hypertension when the organisms reach adulthood and that this elevation in blood pressure is accompanied by OS [ 195 , 196 ].…”

“…SOD reduces the ROS that uncouple eNOS and increase NO levels [ 199 ]. SIRT3 was found to be decreased at the end of a short period near weaning when rats received sucrose [ 195 , 196 ].…”