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1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system.
- Source :
-
Journal of Clinical Investigation . 7/1/2002, Vol. 110 Issue 1, p229-238. 10p. - Publication Year :
- 2002
-
Abstract
- Inappropriate activation of the renin-angiotensin system, which plays a central role in the regulation of blood pressure, electrolyte, and volume homeostasis, may represent a major risk factor for hypertension, heart attack, and stroke. Mounting evidence from clinical studies has demonstrated an inverse relationship between circulating vitamin D levels and the blood pressure and/or plasma renin activity, but the mechanism is not understood. We show here that renin expression and plasma angiotensin II production were increased severalfold in vitamin D receptor-null (VDR-null) mice, leading to hypertension, cardiac hypertrophy, and increased water intake. However, the salt- and volume-sensing mechanisms that control renin synthesis are still intact in the mutant mice. In wild-type mice, inhibition of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] synthesis also led to an increase in renin expression, whereas 1,25(OH)(2)D(3) injection led to renin suppression. We found that vitamin D regulation of renin expression was independent of calcium metabolism and that 1,25(OH)(2)D(3) markedly suppressed renin transcription by a VDR-mediated mechanism in cell cultures. Hence, 1,25(OH)(2)D(3) is a novel negative endocrine regulator of the renin-angiotensin system. Its apparent critical role in electrolytes, volume, and blood pressure homeostasis suggests that vitamin D analogues could help prevent or ameliorate hypertension. [ABSTRACT FROM AUTHOR]
- Subjects :
- *RNA metabolism
*ANIMAL experimentation
*CELL receptors
*CELLULAR signal transduction
*COMPARATIVE studies
*DRINKING behavior
*SODIUM content of food
*GENE expression
*GENES
*HYPERTENSION
*HYPOCALCEMIA
*RESEARCH methodology
*MEDICAL cooperation
*MICE
*NEUROPEPTIDES
*PROTEINS
*RENIN
*RESEARCH
*RESEARCH funding
*RNA
*ANGIOTENSIN II
*EVALUATION research
*RENIN-angiotensin system
*CALCITRIOL
*IN vitro studies
*PHYSIOLOGY
Subjects
Details
- Language :
- English
- ISSN :
- 00219738
- Volume :
- 110
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Journal of Clinical Investigation
- Publication Type :
- Academic Journal
- Accession number :
- 119414452
- Full Text :
- https://doi.org/10.1172/jci0215219