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.
Clin Exp Pharmacol Physiol. 2019 Dec;46(12):1151-1165. doi: 10.1111/1440-1681.13161. Epub 2019 Sep 9.
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 Ca -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 Cr , 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.
母体盐过载会导致后代心血管和肾脏发生改变。然而，高剂量维生素 E 补充在人类和动物中既有有益作用，也有有害作用。我们假设盐过载是否会导致妊娠期间的心血管和肾脏改变，以及在哺乳期和断奶后这些改变是否会进一步改变。雄性 Wistar 大鼠被用于实验，其母亲在妊娠前和妊娠期间分别饮用自来水或 0.3 mol/L NaCl 20 天。在哺乳期，α-生育酚（0.35 g/kg）每天给予母亲，或在断奶后 3 周给予其后代。在 210 天大的幼鼠中测量收缩压（tcSBP）。还检查了静脉内输注血管紧张素 II（Ang II）对平均动脉压（MAP）和心率（HR）的反应。测量左心室质膜（PMCA）和肌浆网 Ca -ATP 酶（SERCA）的活性以及某些肾功能参数。母体盐水编程导致体重和肾脏重量/体重比增加，tcSBP 增加，MAP 和 HR 增加，对输注的 Ang II 反应异常。在心脏中，盐水增加了 PMCA，而α-生育酚本身增加了 PMCA/SERCA。在肾脏中，最显著的结果是沉默的盐水编程 Cr ，在 α-生育酚之后，Cr 急剧下降。总之，母体盐过载与出生后立即补充高浓度α-生育酚相结合，会导致年轻后代同时出现心血管和肾脏改变，就像在 5 型心肾综合征中遇到的改变一样。
