1,25-Dihydroxyvitamin D3 is a negative endocrine regulator of the renin-angiotensin system

Yan Chun Li*, Juan Kong, Minjie Wei, Zhou Feng Chen, Shu Q. Liu, Li Ping Cao

*Corresponding author for this work

Research output: Contribution to journalArticle

1441 Citations (Scopus)

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 D3 [1,25(OH)2D3] synthesis also led to an increase in renin expression, whereas 1,25(OH)2D3 injection led to renin suppression. We found that vitamin D regulation of renin expression was independent of calcium metabolism and that 1,25(OH)2D3 markedly suppressed renin transcription by a VDR-mediated mechanism in cell cultures. Hence, 1,25(OH)2D3 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.

Original languageEnglish (US)
Pages (from-to)229-238
Number of pages10
JournalJournal of Clinical Investigation
Volume110
Issue number2
DOIs
StatePublished - Jan 1 2002

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Calcitriol
Renin-Angiotensin System
Renin
Vitamin D
Blood Pressure
Hypertension
Electrolytes
Homeostasis
Calcitriol Receptors
Cardiomegaly
Blood Volume
Angiotensin II
Drinking
Cell Culture Techniques
Salts
Stroke
Myocardial Infarction
Calcium
Injections

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Li, Yan Chun ; Kong, Juan ; Wei, Minjie ; Chen, Zhou Feng ; Liu, Shu Q. ; Cao, Li Ping. / 1,25-Dihydroxyvitamin D3 is a negative endocrine regulator of the renin-angiotensin system. In: Journal of Clinical Investigation. 2002 ; Vol. 110, No. 2. pp. 229-238.
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1,25-Dihydroxyvitamin D3 is a negative endocrine regulator of the renin-angiotensin system. / Li, Yan Chun; Kong, Juan; Wei, Minjie; Chen, Zhou Feng; Liu, Shu Q.; Cao, Li Ping.

In: Journal of Clinical Investigation, Vol. 110, No. 2, 01.01.2002, p. 229-238.

Research output: Contribution to journalArticle

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