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Clin Exp Pharmacol Physiol. 2019 Dec;46(12):1151-1165. doi: 10.1111/1440-1681.13161. Epub 2019 Sep 9.

Alpha-Tocopherol during lactation and after weaning alters the programming effect of prenatal high salt intake on cardiac and renal functions of adult male offspring.

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Department of Physiology and Pharmacology, Federal University of Pernambuco, Recife, Brazil.
National Center of Structural Biology and Bioimaging/CENABIO, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Department of Pharmacology, Federal University of Paraná, Curitiba, Brazil.
Department of Pathology, Federal University of Pernambuco, Recife, Brazil.
Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
National Institute of Science and Technology for Regenerative Medicine/REGENERA, Rio de Janeiro, Brazil.
Graduate Program in Translational Biomedicine/BIOTRANS, Grande Rio University, Duque de Caxias, Brazil.


Maternal salt overload programs cardiovascular and renal alterations in the offspring. However, beneficial and harmful effects of high dose vitamin E supplementation have been described in humans and animals. We investigated the hypothesis as to whether cardiac and renal alterations can be programmed by gestational salt overload, and can become further modified during lactation and after weaning. Male Wistar rats were used, being the offspring of mothers that drank either tap water or 0.3 mol/L NaCl for 20 days before and during pregnancy. α-Tocopherol (0.35 g/kg) was administered to mothers daily during lactation or to their offspring for 3 weeks post-weaning. Systolic blood pressure (tcSBP) was measured in juvenile rats aged 210 days. The response of mean arterial pressure (MAP) and heart rate (HR) to intravenous infusion of angiotensin II (Ang II) was also examined. Left ventricle plasma membrane (PMCA) and sarcoplasmic reticulum Ca2+ -ATPase (SERCA) activities, and certain parameters of renal function, were measured. Maternal saline programmed for increased body mass and kidney mass/body mass ratio, increased tcSBP, increased mean arterial pressure and heart rate with anomalous response to infused Ang II. In the heart, saline increased PMCA and α-Tocopherol per se increased PMCA/SERCA. In the kidney, the most remarkable result was the silent saline programming of CrCl , which was sensitized for a sharp decrease after α-Tocopherol. In conclusion, the combination of maternal saline overload and high α-Tocopherol immediately after birth leads to simultaneous cardiovascular and renal alterations in the young offspring, like those encountered in type V cardiorenal syndrome.


arterial hypertension; cardiac calcium handling; cardiorenal syndrome; maternal salt overload; α-Tocopherol supplementation


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