Metabolic acidosis has dual effects on sodium handling by rat kidney
Metabolic acidosis has dual effects on sodium handling by rat kidney
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DOI：
10.1152/ajprenal.00338.2005
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发表时间：
2006-08-01
影响因子：
4.2
通讯作者：
Amlal, Hassane
中科院分区：
文献类型：
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作者：
Faroqui, Somia;Sheriff, Sulaiman;Amlal, Hassane
慢性代谢性酸中毒（CMA）与近曲小管（PT）中氯化钠重吸收减少有关。然而，CMA 对远端小管 (DT) 和集合管 (CD) 中 Na+ 转运的影响知之甚少。将大鼠置于代谢笼中，并按照配对喂养方案获得水（对照）、0.28 M NH4Cl 或 0.28 M KCl 溶液，持续 5 天 (5d)。 NH4Cl- 大鼠会在 24 小时内出现代谢性酸中毒，但 KCl 负荷大鼠则不会。有趣的是，处理 24 小时后，NH4Cl 负载的大鼠表现出显着的尿钠排泄，而 KCl 负载的大鼠则没有。尿 Na+ 排泄量从 1.94 meq/24 h 增加至 2.97 meq/24 h (P < 0.001)，并在 CMA 5 天后恢复到低于基线水平 (1.67 meq/l)。皮质Na-Cl协同转运蛋白（NCC）的蛋白质丰度在24小时时保持不变，但在CMA 5天后显着增加（P < 0.01）。皮质中上皮Na+通道（ENaC）的α、β和γ亚基的蛋白质丰度在前24小时内急剧下降，然后在CMA 5天后恢复到基线水平。有趣的是，Sgk1 表达在 24 小时后下降（-31%，P < 0.05），然后在 CMA 5 天后恢复到基线。 Nedd4-2 表达在 CMA 期间没有改变。 CMA 5天后，血清醛固酮水平提高了54%，肾上腺醛固酮合成酶的表达增加了134%。总之，代谢性酸中毒对尿Na+排泄有双重影响。早期尿钠排泄是由于 PT 中 Na+ 重吸收减少以及 DT 和 CD 中与 Sgk1 相关的 ENaC 活性降低所致。醛固酮诱导的 NCC、Sgk1 和 ENaC 上调可能有助于代谢性酸中毒的抗钠尿阶段。这种适应可以防止慢性酸损伤期间 Na+ 的浪费和容量的减少。
Chronic metabolic acidosis (CMA) is associated with decreased NaCl reabsorption in the proximal tubule (PT). However, the effect of CMA on Na+ transport in the distal tubule (DT) and collecting duct (CD) is poorly understood. Rats were placed in metabolic cages and had access to water (control), 0.28 M NH4Cl, or 0.28 M KCl solutions in a pair-feeding protocol for 5 days (5d). Metabolic acidosis developed within 24 h in NH4Cl-, but not in KCl-loaded rats. Interestingly, NH4Cl- but not KCl-loaded rats exhibited a significant natriuresis after 24 h of treatment. Urinary Na+ excretion increased from 1.94 to 2.97 meq/24 h (P < 0.001) and returned to below baseline level (1.67 meq/l) after 5d of CMA. The protein abundance of the cortical Na-Cl cotransporter (NCC) remained unchanged at 24 h, but increased significantly (P < 0.01) after 5d of CMA. The protein abundance of alpha-, beta-, and gamma-subunits of the epithelial Na+ channel (ENaC) in the cortex decreased sharply during the first 24 h and then returned to baseline levels after 5d of CMA. Interestingly, Sgk1 expression decreased after 24 h (-31%, P < 0.05) and then returned to baseline after 5d of CMA. Nedd4-2 expression was not altered during CMA. CMA enhanced serum aldosterone levels by 54% and increased the expression of aldosterone synthase in the adrenal gland by 134% after 5d of CMA. In conclusion, metabolic acidosis has dual effects on urinary Na+ excretion. The early natriuresis results from decreased Na+ reabsorption in the PT and Sgk1-related decreased ENaC activity in the DT and CD. Aldosterone-induced upregulation of NCC, Sgk1, and ENaC likely contributes to the antinatriuretic phase of metabolic acidosis. This adaptation prevents Na+ wasting and volume depletion during chronic acid insult.