Department of Zoology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
Clin Sci (Lond). 2012 Mar;122(6):281-8. doi: 10.1042/CS20110266.
Sodium retention has been proposed as the cause of hypertension in the LP rat (offspring exposed to a maternal low-protein diet in utero) model of developmental programming because of increased renal NKCC2 (Na+/K+/2Cl- co-transporter 2) expression. However, we have shown that LP rats excrete more rather than less sodium than controls, leading us to hypothesize that LP rats ingest more salt in order to maintain sodium balance. Rats were fed on either a 9% (low) or 18% (control) protein diet during pregnancy; male and female offspring were studied at 4 weeks of age. LP rats of both sexes held in metabolism cages excreted more sodium and urine than controls. When given water to drink, LP rats drank more and ate more food than controls, hence sodium intake matched excretion. However, when given a choice between saline and water to drink, the total volume of fluid ingested by LP rats fell to control levels, but the volume of saline taken was significantly larger [3.8±0.1 compared with 8.8±1.3 ml/24 h per 100 g of body weight in control and LP rats respectively; P<0.001]. Interestingly food intake also fell to control levels. Total body sodium content and ECF (extracellular fluid) volumes were greater in LP rats. These results show that prenatal programming of renal sodium wasting leads to a compensatory increase in salt appetite in LP rats. We speculate that the need to maintain salt homoeostasis following malnutrition in utero stimulates greater food intake, leading to accelerated growth and raised BP (blood pressure).
钠潴留被认为是 LP 大鼠(胎儿期暴露于低蛋白饮食的后代)发育编程模型中高血压的原因,因为肾脏 NKCC2(Na+/K+/2Cl-共转运蛋白 2)表达增加。然而,我们已经表明,LP 大鼠排泄的钠比对照组多,而不是少,这导致我们假设 LP 大鼠摄入更多的盐以维持钠平衡。在怀孕期间,大鼠分别喂食 9%(低)或 18%(对照)蛋白质饮食;4 周龄时研究雄性和雌性后代。置于代谢笼中的 LP 大鼠的雌雄两性均排泄出比对照组更多的钠和尿液。当给予水饮用时,LP 大鼠比对照组喝得更多,吃得更多,因此钠的摄入量与排泄量相匹配。然而,当给予 LP 大鼠在盐水和水之间选择饮用时,LP 大鼠摄入的总液体量降至对照水平,但摄入的盐水量明显更大[分别为 3.8±0.1 比 8.8±1.3 ml/24 h/100 g 体重;P<0.001]。有趣的是,食物摄入量也降至对照水平。LP 大鼠的总体钠含量和 ECF(细胞外液)体积增加。这些结果表明,产前编程导致肾脏钠丢失,导致 LP 大鼠盐食欲代偿性增加。我们推测,宫内营养不良后维持盐稳态的需要刺激了更大的食物摄入,导致生长加速和血压升高。