Prenatal programming of renal sodium handling in the rat
Prenatal programming of renal sodium handling in the rat
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DOI：
10.1042/cs20080294
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发表时间：
2009-07-01
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影响因子：
6
通讯作者：
Ashton, Nick
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文献类型：
--
作者：
Alwasel, Saleh H.;Ashton, Nick
母体蛋白限制诱导的产前程序性高血压与肾小管Na+/K+/2Cl（-）协同转运蛋白（NKCC 2）和Na+/Cl-协同转运蛋白（NCC）表达增加有关。这表明肾脏Na+潴留有助于LP大鼠（在子宫内暴露于母体低蛋白饮食的后代）发生高血压。然而，这一假设尚未在体内得到验证。对4周龄高血压雄性和雌性LP大鼠的肾清除率测量表明，尽管肾小球滤过率保持不变，但尿流量（P < 0.01）和尿Na+排泄率（1.6 +/- 0.3和3.0 +/- 0.4 μ mol . min（-1）。100 g（-1）的体重增加（P < 0.001）。Na+排泄量与平均动脉压在雄性（P < 0.01）和雌性（P < 0.05）中均呈正相关，但斜率和截距在对照组和LP组之间均无差异。雄性（对照组和LP大鼠分别为1.5 +/- 0.2和3.0 +/- 0.5%; P < 0.001）和雌性LP大鼠的Na+排泄分数增加，表明肾小管对Na+的重吸收减少。Western blotting和定量PCR结果显示NKCC 2表达增加，而NCC mRNA表达没有上调。Na+/K+ ATP酶α（1）亚单位表达与对照组无差异;然而，全肾泵活性显著降低（23.4 +/- 1.8和17.7 +/- 1.2 nmol磷酸盐）。微克（-1）蛋白质。h（-1）; P < 0.001）;免疫组织化学显示α 1亚单位在髓质内层几乎不存在。LP大鼠的Na+排泄量增加可部分解释为压力-钠尿排泄机制;然而，髓质内Na+/K+ ATP酶α（1）亚单位的丢失和NKCC 2的上调表明，肾脏Na+处理的改变也是产前程序性的。
Prenatally programmed hypertension induced by maternal protein restriction is associated with increased expression of the renal tubular Na+/K+/2Cl(-) co-transporter (NKCC2) and the Na+/Cl- co-transporter (NCC). This has led to the suggestion that renal Na+ retention contributes to the development of hypertension in the LP rat (offspring exposed to a maternal low-protein diet in utero). However, this hypothesis has not been tested in vivo. Renal clearance measurements in hypertensive 4-week-old male and female LP rats showed that, although the glomerular filtration rate remained unaltered, urine flow (P < 0.01) and urinary Na+ excretion rates (1.6 +/- 0.3 and 3.0 +/- 0.4 mu mol . min(-1) . 100 g(-1) of body weight in control male and LP male respectively; P < 0.001) were increased. Na+ excretion was positively correlated with mean arterial pressure in both males (P < 0.01) and females (P < 0.05), but neither the slope nor the intercept differed between control and LP rats. Fractional excretion of Na+ was increased in male (1.5 +/- 0.2 and 3.0 +/- 0.5% in control and LP rats respectively; P < 0.001) and female LP rats, implying reduced tubular reabsorption of Na+. Western blotting and quantitative PCR showed that NKCC2 expression was increased, whereas NCC mRNA was not up-regulated. Na+/K+ ATPase alpha(1) subunit expression did not differ from controls; however, there was a significant reduction in whole kidney pump activity (23.4 +/- 1.8 and 17.7 +/- 1.2 nmol of phosphate . mu g(-1) of protein . h(-1) in control male and male LP rats respectively; P < 0.001); immunohistochemistry showed that the alpha(1) subunit was virtually absent from the inner medulla. The greater Na+ excretion of LP rats can be explained, in part, by a pressure-natriuresis mechanism; however, the loss of the Na+/K+ ATPase alpha(1) subunit from the inner medulla and up-regulation of NKCC2 suggests that altered renal Na+ handling is also programmed prenatally.