Direct and Indirect Mineralocorticoid Effects Determine Distal Salt Transport
| Autor: | David H. Ellison, Bethzaida Yarbrough, Kayla J. Erspamer, Rebecca A. Lazelle, Chao Ling Yang, Mohammed Z. Ferdaus, James A. McCormick, Nicholas P. Meermeier, Andrew S. Terker, Hae J. Park |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Epithelial sodium channel medicine.medical_specialty Hyperkalemia medicine.drug_class Nephron Mice 03 medical and health sciences chemistry.chemical_compound Internal medicine medicine Animals Sodium Chloride Dietary Kidney Tubules Distal Receptor Mice Knockout Aldosterone urogenital system business.industry Biological Transport General Medicine Hypokalemia Receptors Mineralocorticoid Basic Research 030104 developmental biology medicine.anatomical_structure Endocrinology chemistry Nephrology Mineralocorticoid medicine.symptom Cotransporter business |
| Zdroj: | Journal of the American Society of Nephrology. 27:2436-2445 |
| ISSN: | 1533-3450 1046-6673 |
| Popis: | Excess aldosterone is an important contributor to hypertension and cardiovascular disease. Conversely, low circulating aldosterone causes salt wasting and hypotension. Aldosterone activates mineralocorticoid receptors (MRs) to increase epithelial sodium channel (ENaC) activity. However, aldosterone may also stimulate the thiazide-sensitive Na(+)-Cl(-) cotransporter (NCC). Here, we generated mice in which MRs could be deleted along the nephron to test this hypothesis. These kidney-specific MR-knockout mice exhibited salt wasting, low BP, and hyperkalemia. Notably, we found evidence of deficient apical orientation and cleavage of ENaC, despite the salt wasting. Although these mice also exhibited deficient NCC activity, NCC could be stimulated by restricting dietary potassium, which also returned BP to control levels. Together, these results indicate that MRs regulate ENaC directly, but modulation of NCC is mediated by secondary changes in plasma potassium concentration. Electrolyte balance and BP seem to be determined, therefore, by a delicate interplay between direct and indirect mineralocorticoid actions in the distal nephron. |
| Databáze: | OpenAIRE |
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