Renal Division, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
Cells. 2020 Apr 14;9(4):967. doi: 10.3390/cells9040967.
Aldosterone indirectly regulates water reabsorption in the distal tubule by regulating sodium reabsorption. However, the direct effect of aldosterone on vasopressin-regulated water and urea permeability in the rat inner medullary collecting duct (IMCD) has not been tested. We investigated whether aldosterone regulates osmotic water permeability in isolated perfused rat IMCDs. Adding aldosterone (500 nM) to the bath significantly decreased osmotic water permeability in the presence of vasopressin (50 pM) in both male and female rat IMCDs. Aldosterone significantly decreased aquaporin-2 (AQP2) phosphorylation at S256 but did not change it at S261. Previous studies show that aldosterone can act both genomically and non-genomically. We tested the mechanism by which aldosterone attenuates osmotic water permeability. Blockade of gene transcription with actinomycin D did not reverse aldosterone-attenuated osmotic water permeability. In addition to AQP2, the urea transporter UT-A1 contributes to vasopressin-regulated urine concentrating ability. We tested aldosterone-regulated urea permeability in vasopressin-treated IMCDs. Blockade of gene transcription did not reverse aldosterone-attenuated urea permeability. In conclusion, aldosterone directly regulates water reabsorption through a non-genomic mechanism. Aldosterone-attenuated water reabsorption may be related to decreased trafficking of AQP2 to the plasma membrane. There may be a sex difference apparent in the inhibitory effect of aldosterone on water reabsorption in the inner medullary collecting duct. This study is the first to show a direct effect of aldosterone to inhibit vasopressin-stimulated osmotic water permeability and urea permeability in perfused rat IMCDs.
醛固酮通过调节钠重吸收间接调节远端肾小管的水重吸收。然而，醛固酮对大鼠内髓集合管（IMCD）中血管加压素调节的水和尿素通透性的直接影响尚未得到检验。我们研究了醛固酮是否调节分离灌注的大鼠 IMCD 中的渗透水通透性。在血管加压素（50 pM）存在的情况下，向浴液中添加醛固酮（500 nM）可显著降低雄性和雌性大鼠 IMCD 中的渗透水通透性。醛固酮显著降低 AQP2 在 S256 的磷酸化，但在 S261 没有改变。先前的研究表明，醛固酮可以通过基因组和非基因组途径发挥作用。我们测试了醛固酮减弱渗透水通透性的机制。用放线菌素 D 阻断基因转录并没有逆转醛固酮减弱的渗透水通透性。除 AQP2 外，尿素转运蛋白 UT-A1 有助于血管加压素调节的尿液浓缩能力。我们测试了血管加压素处理的 IMCD 中醛固酮调节的尿素通透性。基因转录阻断没有逆转醛固酮减弱的尿素通透性。总之，醛固酮通过非基因组机制直接调节水重吸收。醛固酮减弱的水重吸收可能与 AQP2 向质膜的转运减少有关。在 IMCD 中，醛固酮对水重吸收的抑制作用可能存在性别差异。本研究首次表明，醛固酮对灌注大鼠 IMCD 中血管加压素刺激的渗透水通透性和尿素通透性有直接抑制作用。
