1,25-Dihydroxyvitamin D3 is a negative endocrine regulator of the renin-angiotensin system
Open accessAbstract
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.
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- Authors
- Li, Y. C., Kong, J., Wei, M., Chen, Z.-F., Liu, S. Q., & Cao, L.-P.
- Affiliations
- University of Chicago (US)
- Washington University in St. Louis (US)
- Northwestern University (US)
- Corresponding author
- Li, Yan Chun
- Venue
- Journal of Clinical Investigation
- Published
- 2002-07-15
- Volume
- 110
- Issue
- 2
- Pages
- 229-238
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W4233469193
- Cited by
- 1,625
- References
- 40
- Citations by year
- 2026: 18 · 2025: 36 · 2024: 41 · 2023: 57 · 2022: 71 · 2021: 81 · 2020: 93 · 2019: 72 · 2018: 79 · 2017: 94 · 2016: 80 · 2015: 87 · 2014: 98 · 2013: 100 · 2012: 106
- FWCI
- 17.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Pathology and Forensic Medicine › Vitamin D Research Studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Keywords
- 1,25-dihydroxyvitamin D3, vitamin D receptor, renin-angiotensin system, renin expression, angiotensin II, hypertension, cardiac hypertrophy, water intake, blood pressure homeostasis, vitamin D analogs
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