Back to Search
Start Over
Potassium deficiency decreases the capacity for urea synthesis and markedly increases ammonia in rats
- Source :
- Mikkelsen, A C D, Thomsen, K L, Vilstrup, H V A, Aamann, L, Jones, H, Mookerjee, R P, Hamilton-Dutoit, S J, Frystyk, J & Aagaard, N K 2021, ' Potassium deficiency decreases the capacity for urea synthesis and markedly increases ammonia in rats ', American Journal of Physiology: Gastrointestinal and Liver Physiology, vol. 320, no. 4 . https://doi.org/10.1152/ajpgi.00136.2020
- Publication Year :
- 2021
-
Abstract
- Our study provides novel findings of experimental hypokalemia reducing urea cycle functionality and thereby severely increasing plasma ammonia. This is pathophysiologically interesting because plasma ammonia increases during hypokalemia by a hitherto unknown mechanism, which may be particular important in relation to the unexplained link between hypokalemia and hepatic encephalopathy. 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. Female Wistar rats were fed a potassium-free diet for 13 days. Half of the rats were then potassium repleted. Both groups were compared with 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. The diet induced hypokalemia of 1.9 ± 0.4 mmol/L. Compared with 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. 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.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Physiology
Hypokalemia
Kidney
Gene Expression Regulation, Enzymologic
03 medical and health sciences
Ammonia
chemistry.chemical_compound
0302 clinical medicine
Physiology (medical)
Internal medicine
medicine
Animals
Hyperammonemia
Urea
Rats, Wistar
Muscle, Skeletal
Potassium Deficiency
Hepatology
Chemistry
Gastroenterology
Potassium, Dietary
medicine.disease
Disease Models, Animal
030104 developmental biology
Endocrinology
Liver
Urea cycle
Potassium
Female
030211 gastroenterology & hepatology
Potassium deficiency
medicine.symptom
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Mikkelsen, A C D, Thomsen, K L, Vilstrup, H V A, Aamann, L, Jones, H, Mookerjee, R P, Hamilton-Dutoit, S J, Frystyk, J & Aagaard, N K 2021, ' Potassium deficiency decreases the capacity for urea synthesis and markedly increases ammonia in rats ', American Journal of Physiology: Gastrointestinal and Liver Physiology, vol. 320, no. 4 . https://doi.org/10.1152/ajpgi.00136.2020
- Accession number :
- edsair.doi.dedup.....58ed3967bb5967a657e132beaa5d6204