母体蛋白限制导致雄性后代对压力和盐敏感性高血压的反应过度。
Maternal protein restriction leads to hyperresponsiveness to stress and salt-sensitive hypertension in male offspring.
机构信息
Department of Medicine, Wayne State University, Detroit, MI, USA.
出版信息
Am J Physiol Regul Integr Comp Physiol. 2010 May;298(5):R1375-82. doi: 10.1152/ajpregu.00848.2009. Epub 2010 Mar 3.
Low birth weight humans often exhibit hypertension during adulthood. Studying the offspring of rat dams fed a maternal low-protein diet is one model frequently used to study the mechanisms of low birth weight-related hypertension. It remains unclear whether this model replicates key clinical findings of hypertension and increased blood pressure responsiveness to stress or high-salt diet. We measured blood pressure via radiotelemetry in 13-wk-old male offspring of maternal normal- and low-protein dams. Neither group exhibited hypertension at baseline; however, 1 h of restraint was accompanied by a significantly greater blood pressure response in low-protein compared with normal-protein offspring. To enhance the effect of a high-salt diet on blood pressure, normal- and low-protein offspring underwent right uninephrectomy, while controls underwent sham surgery. After 5 weeks on a high-salt diet (4% NaCl), mean arterial pressure in the Low-Protein+Sham offspring was elevated by 6 +/- 2 mmHg (P < 0.05 vs. baseline), while it remained unchanged in the normal-protein offspring. In the two uninephrectomized groups, blood pressure increased further, but was of similar magnitude. Glomerular filtration rate in the low-protein uninephrectomized offspring was 50% less than that in normal-protein offspring with intact kidneys. These data indicate that, while male low-protein offspring are not hypertensive during young adulthood, their blood pressure is hyperresponsive to restraint stress and is salt sensitive, and their glomerular filtration rate is more sensitive to hypertension-causing insults. Collectively, these may predispose for the development of hypertension later in life.
低出生体重的人类在成年后通常会出现高血压。研究母体低蛋白饮食喂养的大鼠后代是研究低出生体重相关高血压机制的常用模型之一。目前尚不清楚该模型是否复制了高血压和对压力或高盐饮食的血压反应性增加的关键临床发现。我们通过无线电遥测法测量了母体正常蛋白和低蛋白饮食喂养的大鼠后代 13 周龄雄性幼崽的血压。两组在基线时均未出现高血压;然而,与正常蛋白组相比,低蛋白组在 1 小时的束缚应激后血压反应明显更大。为了增强高盐饮食对血压的影响,正常蛋白和低蛋白组的幼崽接受了单侧肾切除术,而对照组接受了假手术。在高盐饮食(4%NaCl)下 5 周后,低蛋白+假手术组的平均动脉压升高了 6 +/- 2mmHg(P < 0.05 与基线相比),而正常蛋白组的血压则保持不变。在两个单侧肾切除组中,血压进一步升高,但幅度相似。低蛋白单侧肾切除组的肾小球滤过率比正常蛋白组的有完整肾脏的幼崽低 50%。这些数据表明,虽然低蛋白饮食的雄性幼崽在青年期没有高血压,但它们的血压对束缚应激反应过度,对盐敏感,其肾小球滤过率对引起高血压的损伤更为敏感。总的来说,这些可能会导致他们以后更容易患上高血压。