Background and Aims: Potassium deficiency decreases gene expression, protein synthesis, and growth. The urea cycle maintains body nitrogen homeostasis including removal of toxic ammonia. Hyperammonemia is an obligatory trait of liver failure, increasing the risk for hepatic encephalopathy, and hypokalemia is reported to increase ammonia. We aimed to clarify the effects of experimental hypokalemia on the in vivo capacity of the urea cycle, on the genes of the enzymes involved, and on ammonia concentrations. Method: Female Wistar rats were fed a potassium free diet for 13 days. Half of the rats were then potassium repleted. Both groups were compared to pair- and free-fed controls. The following were measured: in vivo capacity of urea-nitrogen synthesis (CUNS); gene expression (mRNA) of urea cycle enzymes; plasma potassium, sodium, and ammonia; intracellular potassium, sodium, and magnesium in liver, kidney, and muscle tissues, and liver sodium/potassium pumps. Liver histology was assessed. Results: The diet induced hypokalemia of 1.9±0.4 mmol/L. Compared to pair-fed controls, the in vivo CUNS was reduced by 34% (p<0.01), gene expression of argininosuccinate synthetase 1 (ASS1) was decreased by 33% (p<0.05), and plasma ammonia concentrations were eightfold elevated (p<0.001). Kidney and muscle tissue potassium contents were markedly decreased, but unchanged in liver tissue. Protein expressions of liver sodium/potassium pumps were unchanged. Repletion of potassium reverted all the changes. Conclusion: Hypokalemia decreased the capacity for urea synthesis via gene effects. The intervention led to marked hyperammonemia, quantitatively explainable by the compromised urea cycle. Our findings motivate clinical studies of patients with liver disease.

中文翻译：

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缺钾会降低大鼠的尿素合成能力并显着增加氨


背景和目的：钾缺乏会降低基因表达、蛋白质合成和生长。尿素循环维持体内氮稳态，包括去除有毒氨。高氨血症是肝功能衰竭的必然特征，会增加肝性脑病的风险，据报道低钾血症会增加氨。我们的目的是阐明实验性低钾血症对体内尿素循环能力、相关酶基因以及氨浓度的影响。方法：用无钾饮食喂养雌性 Wistar 大鼠 13 天。然后给一半的大鼠补充钾。两组均与配对和自由喂养对照组进行比较。测量以下内容：体内尿素氮合成能力（CUNS）；尿素循环酶的基因表达（mRNA）；血浆钾、钠和氨；肝脏、肾脏和肌肉组织中的细胞内钾、钠和镁，以及肝脏钠/钾泵。评估肝脏组织学。结果：饮食引起的低钾血症为1.9±0.4 mmol/L。与配对喂养对照相比，体内 CUNS 降低了 34%（p<0.01），精氨基琥珀酸合成酶 1 (ASS1) 的基因表达降低了 33%（p<0.05），血浆氨浓度升高了八倍（ p<0.001）。肾脏和肌肉组织钾含量显着降低，但肝组织钾含量无变化。肝脏钠/钾泵的蛋白质表达没有变化。补充钾可以恢复所有的变化。结论：低钾血症通过基因效应降低尿素合成能力。干预导致明显的高氨血症，这可以通过尿素循环受损来定量解释。我们的研究结果推动了肝病患者的临床研究。