Bédard Sophie, Sicotte Benoit, St-Louis Jean, Brochu Michèle
Centre de Recherche, Department of Obstetrics-Gynecology, Université de Montréal, Hôpital Sainte-Justine, 3175 Côte Ste-Catherine, Montréal, Québec, Canada H3T 1C5.
J Physiol. 2005 Feb 1;562(Pt 3):937-50. doi: 10.1113/jphysiol.2004.064683. Epub 2004 Nov 11.
We previously reported that sodium restriction during pregnancy reduces plasma volume expansion and promotes intra-uterine growth restriction (IUGR) in rats while it activates the renin-angiotensin-aldosterone system (RAAS). In the present study, we proceeded to determine whether expression of the two angiotensin II (ANGII) receptor subtypes (AT(1) and AT(2)) change in relation to maternal water-electrolyte homeostasis and fetal growth. To this end, pregnant (gestation day 15) and non-pregnant Sprague-Dawley rats were randomly assigned to two groups fed either normal, or Na(+)-restricted diets for 7 days. At the end of the treatment period, plasma aldosterone and renin activity as well as plasma and urine electrolytes were measured. Determinations for AT(1) and AT(2) mRNA and protein were made by RNase protection assay and photoaffinity labelling, respectively, using a number of tissues implicated in volume regulation and fetal growth. In non-pregnant rats, Na(+) restriction decreases Na(+) excretion without altering plasma volume, plasma Na(+) concentration or the expression of AT(1) and AT(2) mRNA or protein in the tissues examined. In normally fed pregnant rats when compared to non-pregnant controls, AT(1) mRNA increases in the hypothalamus as well as pituitary and declines in uterine arteries, while AT(1) protein decreases in the kidney and AT(2) mRNA declines in the adrenal cortex. In pregnant rats, Na(+) restriction induces a decrease in plasma Na(+), an increase in plasma urea, as well as a decline in renal urea and creatinine clearance rates. Protein levels for both AT(1) and AT(2) in the pituitary and AT(2) mRNA in the adrenal cortex are lower in the Na(+)-restricted pregnant group when compared to normally fed pregnant animals. Na(+) restriction also induces a decrease in AT(1) protein in the placenta. In conclusion, these results suggest that pregnancy may increase sensitivity to Na(+) depletion by the tissue-specific modulation of ANGII receptors. Finally, these receptors may be implicated in the IUGR response to low Na(+).
我们之前报道过，孕期限制钠摄入会减少大鼠的血浆容量扩张，促进子宫内生长受限（IUGR），同时激活肾素 - 血管紧张素 - 醛固酮系统（RAAS）。在本研究中，我们进一步确定两种血管紧张素II（ANGII）受体亚型（AT(1)和AT(2)）的表达是否会随着母体水电解质平衡和胎儿生长而发生变化。为此，将怀孕（妊娠第15天）和未怀孕的Sprague-Dawley大鼠随机分为两组，分别给予正常饮食或限钠饮食7天。在治疗期结束时，测量血浆醛固酮和肾素活性以及血浆和尿液电解质。分别使用多种参与容量调节和胎儿生长的组织，通过核糖核酸酶保护分析和光亲和标记法测定AT(1)和AT(2)的mRNA和蛋白质。在未怀孕的大鼠中，限钠会减少钠排泄，但不会改变血浆容量、血浆钠浓度或所检测组织中AT(1)和AT(2)的mRNA或蛋白质表达。与未怀孕的对照组相比，正常饮食的怀孕大鼠中，下丘脑以及垂体中的AT(1) mRNA增加，子宫动脉中的AT(1) mRNA下降，而肾脏中的AT(1)蛋白质减少，肾上腺皮质中的AT(2) mRNA下降。在怀孕大鼠中，限钠会导致血浆钠减少、血浆尿素增加，以及肾尿素和肌酐清除率下降。与正常饮食的怀孕动物相比，限钠的怀孕组中垂体中AT(1)和AT(2)的蛋白质水平以及肾上腺皮质中AT(2)的mRNA水平较低。限钠还会导致胎盘中AT(1)蛋白质减少。总之，这些结果表明，怀孕可能通过对ANGII受体的组织特异性调节增加对钠缺乏的敏感性。最后，这些受体可能与IUGR对低钠的反应有关。
