Back to Search
Start Over
Loss of vitamin D receptor produces polyuria by increasing thirst.
- Source :
-
Journal of the American Society of Nephrology : JASN [J Am Soc Nephrol] 2008 Dec; Vol. 19 (12), pp. 2396-405. Date of Electronic Publication: 2008 Oct 02. - Publication Year :
- 2008
-
Abstract
- Vitamin D receptor (VDR)-null mice develop polyuria, but the underlying mechanism remains unknown. In this study, we investigated the relationship between vitamin D and homeostasis of water and electrolytes. VDR-null mice had polyuria, but the urine osmolarity was normal as a result of high salt excretion. The urinary responses to water restriction and to vasopressin were similar between wild-type and VDR-null mice, suggesting intact fluid-handling capacity in VDR-null mice. Compared with wild-type mice, however, renin and angiotensin II were dramatically upregulated in the kidney and brain of VDR-null mice, leading to a marked increase in water intake and salt appetite. Angiotensin II-mediated upregulation of intestinal NHE3 expression partially explained the increased salt absorption and excretion in VDR-null mice. In the brain of VDR-null mice, expression of c-Fos, which is known to associate with increased water intake, was increased in the hypothalamic paraventricular nucleus and the subfornical organ. Treatment with an angiotensin II type 1 receptor antagonist normalized water intake, urinary volume, and c-Fos expression in VDR-null mice. Furthermore, despite a salt-deficient diet to reduce intestinal salt absorption, VDR-null mice still maintained the increased water intake and urinary output. Together, these data indicate that the polyuria observed in VDR-null mice is not caused by impaired renal fluid handling or increased intestinal salt absorption but rather is the result of increased water intake induced by the increase in systemic and brain angiotensin II.
- Subjects :
- Angiotensin II metabolism
Animals
Gene Expression Regulation
Losartan pharmacology
Mice
Mice, Inbred C57BL
Polyuria etiology
Proto-Oncogene Proteins c-fos metabolism
Renin blood
Reverse Transcriptase Polymerase Chain Reaction
Salts pharmacology
Sodium-Hydrogen Exchanger 3
Sodium-Hydrogen Exchangers metabolism
Up-Regulation
Polyuria genetics
Polyuria pathology
Receptors, Calcitriol genetics
Receptors, Calcitriol physiology
Thirst
Subjects
Details
- Language :
- English
- ISSN :
- 1533-3450
- Volume :
- 19
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Journal of the American Society of Nephrology : JASN
- Publication Type :
- Academic Journal
- Accession number :
- 18832438
- Full Text :
- https://doi.org/10.1681/ASN.2008010011