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.
Highlights
Arterial hypertension is considered to be one of the main problems in global public health
We evaluated whether the polyphenol mixture might determine Sirtuin 1 (SIRT1) and Sirtuin 3 (SIRT3) expression modulating endothelial nitric oxide synthase (eNOS) expression and oxidative stress in blood vessels
The increase in SIRT1 found in this study in response to the RSV/QSC treatment is in agreement with the results previously reported by Peredo et al [10], who observed an elevation in the expression of this protein after 1 month of treatment with RSV/QSC in rat adipose tissue
Summary
Arterial hypertension is considered to be one of the main problems in global public health. It is defined as a systolic pressure above 140 mmHg and a diastolic pressure above 90 mmHg, and it is estimated that 40% of the population aged 25 or over has hypertension. The presence of hypertension increases the risk of developing cardiomyopathies, renal insufficiency, and cerebrovascular accidents [1]. This disease may be related to other pathologies, such as diabetes, metabolic syndrome (MS), and obesity, and several causes predispose the population to develop it, such as the genetic predisposition and unhealthy lifestyles. We have reported that sucrose ingestion for 6 months after weaning in rats results in MS which is accompanied by a high blood pressure [3]
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