Effect of Sucrose Ingestion at the End of a Critical Window that Increases Hypertension Susceptibility on Peripheral Mechanisms Regulating Blood Pressure in Rats. Role of Sirtuins 1 and 3

Susceptibility to develop hypertension may be established during early stages of life that include the intrauterine period, infancy and childhood. We recently showed that blood pressure increased when rats reached adulthood when sucrose was ingested for a short-term critical window from postnatal day 12 to 28 in the rat, which corresponds to days around weaning. Here, we studied several factors that might participate in the increased susceptibility to hypertension when adulthood is reached by analyzing the changes produced at the end of the sucrose ingestion during this critical period. Body weight of the rats at the end of the sucrose period was decreased even if there was an increased ingestion in Kcal. We found an increase in blood pressure accompanied by a decrease in endothelial nitric oxide synthase (eNOS) expression in the aorta. When insulin was administered to rats receiving sucrose, glucose in plasma diminished later than in controls and this slight insulin resistance may reduce nitric oxide synthase action. Oleic acid that modulates eNOS expression was increased, lipoperoxidation was elevated and total non-enzymatic anti-oxidant capacity was decreased. There was also a decrease in SOD2 expression. We also studied the expression of Sirt1, which regulates eNOS expression and Sirt3, which regulates SOD2 expression as possible epigenetic targets of enzyme expression involved in the long- term programming of hypertension. Sirt3 was decreased but we did not find an alteration in Sirt1 expression. We conclude that these changes may underpin the epigenetic programming of increased susceptibility to develop hypertension in the adults when there was exposure to high sucrose levels near weaning in rats.