Mansuri Asifhusen, Elmaghrabi Ayah, Legan Susan K, Gattineni Jyothsna, Baum Michel
Department of Pediatrics University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
Department of Internal Medicine University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
PLoS One. 2015 Dec 31;10(12):e0146183. doi: 10.1371/journal.pone.0146183. eCollection 2015.
Maternal low protein diet programs offspring to develop hypertension as adults. Transient exposure to angiotensin converting enzyme inhibitors or angiotensin II receptor blockers can result in improvement in hypertension. Male rats whose mothers received a low protein diet during the last half of pregnancy were given either vehicle, continuous enalapril (CE) in their drinking water or were given transient enalapril exposure (TE) after weaning at 21 days of age. The TE group had enalapril in their drinking water for 21 days starting from day 21 of life. All rats were studied at 6 months of age. Vehicle treated rats whose mothers were fed a low protein diet were hypertensive, had albuminuria, and demonstrated upregulation of the intrarenal renin-angiotensin system as evidenced by higher urinary angiotensinogen and urinary angiotensin II levels. In low protein rats both continuous and transient exposure to enalapril normalized blood pressure, urinary angiotensinogen and urinary angiotensin II levels at 6 months of age, but only continuous administration of enalapril decreased urinary albumin excretion. These data support the importance of the intrarenal renin-angiotensin system in mediating hypertension in programmed rats and transient exposure to enalapril can reprogram the hypertension and dysregulation of the intrarenal renin-angiotensin system.
母体低蛋白饮食会使后代成年后易患高血压。短暂接触血管紧张素转换酶抑制剂或血管紧张素II受体阻滞剂可使高血压病情得到改善。在妊娠后半期其母亲接受低蛋白饮食的雄性大鼠，分别给予赋形剂、饮水中持续添加依那普利（CE）或在21日龄断奶后给予短暂依那普利暴露（TE）。TE组从出生第21天起在饮水中添加依那普利，持续21天。所有大鼠均在6月龄时进行研究。其母亲喂食低蛋白饮食的接受赋形剂治疗的大鼠患有高血压、蛋白尿，并且肾内肾素-血管紧张素系统上调，尿血管紧张素原和尿血管紧张素II水平升高证明了这一点。在低蛋白饮食的大鼠中，持续和短暂接触依那普利均可使6月龄时的血压、尿血管紧张素原和尿血管紧张素II水平恢复正常，但只有持续给予依那普利可降低尿白蛋白排泄。这些数据支持肾内肾素-血管紧张素系统在介导程序化大鼠高血压中的重要性，短暂接触依那普利可重新编程高血压及肾内肾素-血管紧张素系统的失调。
