Impaired renal HCO 3 − secretion in CFTR deficient mice causes metabolic alkalosis during chronic base‐loading
| Autor: | Helle A. Praetorius, Samuel L Svendsen, Mads V. Sorensen, Thi Thuy Linh Hoang, Peder Berg, Jens Leipziger |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Physiology Urinary system Metabolic alkalosis 030204 cardiovascular system & hematology Cystic fibrosis Excretion 03 medical and health sciences HCO3- homeostasis 0302 clinical medicine Urinary HCO3- excretion In vivo Internal medicine medicine Pendrin CFTR biology Chemistry medicine.disease 030104 developmental biology Endocrinology biology.protein Net acid excretion Homeostasis |
| Zdroj: | Berg, P, Svendsen, S L, Hoang, T T L, Praetorius, H A, Sørensen, M V & Leipziger, J 2021, ' Impaired renal HCO 3-secretion in CFTR deficient mice causes metabolic alkalosis during chronic base-loading ', Acta Physiologica, vol. 231, no. 3, e13591 . https://doi.org/10.1111/apha.13591 |
| ISSN: | 1748-1716 1748-1708 |
| DOI: | 10.1111/apha.13591 |
| Popis: | Aim: Cystic fibrosis patients have an increased risk of developing metabolic alkalosis presumably as a result of altered renal HCO3- handling. In this study, we directly assess the kidneys’ ability to compensate for a chronic base-load in the absence of functional CFTR. Methods: Comprehensive urine and blood acid-base analyses were done in anesthetized WT mice or mice lacking either CFTR or pendrin, with or without 7 days of oral NaHCO3 loading. The in vivo experiments were complemented by a combination of immunoblotting and experiments with perfused isolated mouse cortical collecting ducts (CCD). Results: Base-loaded WT mice maintained acid-base homeostasis by elevating urinary pH and HCO3- excretion and decreasing urinary net acid excretion. In contrast, pendrin KO mice and CFTR KO mice were unable to increase urinary pH and HCO3- excretion and unable to decrease urinary net acid excretion sufficiently and thus developed metabolic alkalosis in response to the same base-load. The expression of pendrin was increased in response to the base-load in WT mice with a paralleled increased pendrin function in the perfused CCD. In CFTR KO mice, 7 days of base-loading did not upregulate pendrin expression and apical Cl-/HCO3- exchange function was strongly blunted in the CCD. Conclusion: CFTR KO mice develop metabolic alkalosis during a chronic base-load because they are unable to sufficiently elevate renal HCO3- excretion. This can be explained by markedly reduced pendrin function in the absence of CFTR. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|