Endocrine Hypertension Research Centre, University of Queensland Diamantina Institute, Greenslopes and Princess Alexandra Hospitals, Brisbane, Australia.
Department of Nephrology, Royal Brisbane and Women's Hospital, Brisbane, Australia.
Kidney360. 2022 Mar 1;3(5):910-921. doi: 10.34067/KID.0000362022. eCollection 2022 May 26.
Sodium chloride (NaCl) loading and volume expansion suppress the renin-angiotensin-aldosterone system to reduce renal tubular reabsorption of NaCl and water, but effects on the sodium-chloride cotransporter (NCC) and relevant renal transmembrane proteins that are responsible for this modulation in humans are less well investigated.
We used urinary extracellular vesicles (uEVs) as an indirect readout to assess renal transmembrane proteins involved in NaCl and water homeostasis in 44 patients with hypertension who had repeatedly raised aldosterone/renin ratios undergoing infusion of 2 L of 0.9% saline over 4 hours.
When measured by mass spectrometry in 13 patients, significant decreases were observed in NCC (median fold change [FC]=0.70); pendrin (FC=0.84); AQP2 (FC=0.62); and uEV markers, including ALIX (FC=0.65) and TSG101 (FC=0.66). Immunoblotting reproduced the reduction in NCC (FC=0.54), AQP2 (FC=0.42), ALIX (FC=0.52), and TSG101 (FC=0.55) in the remaining 31 patients, and demonstrated a significant decrease in phosphorylated NCC (pNCC; FC=0.49). However, after correction for ALIX, the reductions in NCC (FC=0.90) and pNCC (FC=1.00) were no longer apparent, whereas the significant decrease in AQP2 persisted (FC=0.62).
We conclude that () decreases in NCC and pNCC, induced by acute NaCl loading and volume expansion, may be due to diluted post-test urines; () the lack of change of NCC and pNCC when corrected for ALIX, despite a fall in plasma aldosterone, may be due to the lack of change in plasma K; and () the decrease in AQP2 may be due to a decrease in vasopressin in response to volume expansion.
氯化钠（NaCl）负荷和容量扩张抑制肾素-血管紧张素-醛固酮系统，减少肾近端小管对 NaCl 和水的重吸收，但对人类中负责这种调节的钠-氯共转运蛋白（NCC）和相关的肾跨膜蛋白的影响研究较少。
我们使用尿细胞外囊泡（uEVs）作为间接读数，评估 44 例高血压患者的肾跨膜蛋白，这些患者的醛固酮/肾素比值反复升高，接受 4 小时内输注 2 升 0.9%生理盐水。
在 13 名患者中通过质谱法测量时，观察到 NCC（中位数折叠变化 [FC]=0.70）；pendrin（FC=0.84）；AQP2（FC=0.62）；和 uEV 标志物，包括 ALIX（FC=0.65）和 TSG101（FC=0.66）。免疫印迹在其余 31 名患者中重现了 NCC（FC=0.54）、AQP2（FC=0.42）、ALIX（FC=0.52）和 TSG101（FC=0.55）的减少，并证明磷酸化 NCC（pNCC；FC=0.49）显著减少。然而，在校正 ALIX 后，NCC（FC=0.90）和 pNCC（FC=1.00）的减少不再明显，而 AQP2 的显著减少仍然存在（FC=0.62）。
我们得出结论，（）急性 NaCl 负荷和容量扩张诱导的 NCC 和 pNCC 减少可能是由于尿液稀释后测试；（）尽管血浆醛固酮下降，但在校正 ALIX 后 NCC 和 pNCC 没有变化，可能是由于血浆 K 没有变化；（）AQP2 的减少可能是由于容量扩张引起的抗利尿激素减少。
