Li · The Journal of clinical investigation 2002 · animal and in vitro mechanistic study · n=?

1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system.

Cited 1831 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Bench and animal research (mouse models and in vitro cell culture)

PubMed 12122115 · doi:10.1172/JCI15219 · record verified 2026-08-30

What was done

The authors investigated the molecular mechanism linking vitamin D and the renin-angiotensin system using vitamin D receptor-null (VDR-null) mice, wild-type mice treated with 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] or synthesis inhibitors, and in vitro cell cultures.

What was found

Renin expression and plasma angiotensin II production were increased severalfold in VDR-null mice, resulting in hypertension, cardiac hypertrophy, and increased water intake, while salt- and volume-sensing controls remained intact. In wild-type mice, inhibiting 1,25(OH)(2)D(3) synthesis increased renin expression, whereas 1,25(OH)(2)D(3) injection suppressed it. In cell cultures, 1,25(OH)(2)D(3) suppressed renin transcription via a VDR-mediated mechanism independent of calcium metabolism. Exact numerical values were not reported in the abstract.

Why it matters

This study identifies active vitamin D as a direct negative endocrine regulator of renin gene expression, providing a mechanistic explanation for observed clinical links between low vitamin D and hypertension.

Limits

The study is restricted to animal models and in vitro cell assays without human clinical testing. Sample sizes, quantitative blood pressure values, and exact fold changes are not reported in the abstract.

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