The impact of maternal protein restriction during rat pregnancy upon renal expression of angiotensin receptors and vasopressin-related aquaporins.
The impact of maternal protein restriction during rat pregnancy upon renal expression of angiotensin receptors and vasopressin-related aquaporins.
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DOI：
10.1186/1477-7827-8-105
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发表时间：
2010-08-31
期刊：
影响因子：
--
通讯作者：
McMullen S
中科院分区：
文献类型：
--
作者：
Cornock R;Langley-Evans SC;Mobasheri A;McMullen S
已知大鼠妊娠期间母体蛋白质限制会影响胎儿发育、生长和以后的疾病风险。了解蛋白质营养不良如何影响正常的母体妊娠适应性是有意义的。在这里，我们研究了在正常和减少血浆容量扩张的情况下，妊娠期间调节肾脏血流动力学和血浆容量的机制。该研究的重点是肾血管紧张素受体（ATR）和加压素相关水通道蛋白（AQP）的表达，假设这些蛋白质平衡的改变与妊娠本身以及低蛋白饮食大鼠血浆容量扩张受损相关。雌性Wistar大鼠交配，并在妊娠期间喂食对照（18%酪蛋白）或低蛋白（9%酪蛋白）饮食。在妊娠第5、10、15和20天麻醉动物（n = 8/组/时间点），在人道处死和收集组织前使用Evans Blue染料测定血浆体积。采用PCR和Western blotting检测ATR亚型和AQP 2、3、4在母肾中的表达。24只非妊娠Wistar大鼠在发情周期的规定时间点进行相同的程序。正如预期，妊娠与血容量增加相关，血液稀释影响红细胞计数和血红蛋白浓度。血管紧张素II受体和水通道蛋白2、3和4的表达在发情周期的所有阶段都是稳定的。有趣的模式，肾内蛋白质的表达，观察到怀孕，包括一个显着下调AQP 2。与之前的文献相反，尽管低蛋白喂养大鼠的血容量扩张明显延迟，但妊娠动物组之间的血容量没有显著差异。然而，在低蛋白质喂养的动物中观察到AT 2 R蛋白表达的显著下调以及肌酐清除率的降低。参与妊娠诱导的血浆容量扩张的调节系统易受母体蛋白质限制的影响。
Maternal protein restriction during rat pregnancy is known to impact upon fetal development, growth and risk of disease in later life. It is of interest to understand how protein undernutrition influences the normal maternal adaptation to pregnancy. Here we investigated the mechanisms regulating renal haemodynamics and plasma volume during pregnancy, in the context of both normal and reduced plasma volume expansion. The study focused on expression of renal angiotensin receptors (ATR) and vasopressin-related aquaporins (AQP), hypothesising that an alteration in the balance of these proteins would be associated with pregnancy per se and with compromised plasma volume expansion in rats fed a low-protein diet. Female Wistar rats were mated and fed a control (18% casein) or low-protein (9% casein) diet during pregnancy. Animals were anaesthetised on days 5, 10, 15 and 20 of gestation (n = 8/group/time-point) for determination of plasma volume using Evans Blue dye, prior to euthanasia and collection of tissues. Expression of the ATR subtypes and AQP2, 3 and 4 were assessed in maternal kidneys by PCR and western blotting. 24 non-pregnant Wistar rats underwent the same procedure at defined points of the oestrous cycle. As expected, pregnancy was associated with an increase in blood volume and haemodilution impacted upon red blood cell counts and haemoglobin concentrations. Expression of angiotensin II receptors and aquaporins 2, 3 and 4 was stable across all stages of the oestrus cycle. Interesting patterns of intra-renal protein expression were observed in response to pregnancy, including a significant down-regulation of AQP2. In contrast to previous literature and despite an apparent delay in blood volume expansion in low-protein fed rats, blood volume did not differ significantly between groups of pregnant animals. However, a significant down-regulation of AT2R protein expression was observed in low-protein fed animals alongside a decrease in creatinine clearance. Regulatory systems involved in the pregnancy-induced plasma volume expansion are susceptible to the effects of maternal protein restriction.
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