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

1496 Scopus citations

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

ASJC Scopus subject areas

  • Medicine(all)

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