Vitamin D: a negative endocrine regulator of the renin-angiotensin system and blood pressure.
The renin-angiotensin system (RAS) plays a central role in the regulation of blood pressure, volume and electrolyte homeostasis. Inappropriate activation of the RAS may lead to hypertension. Clinical and epidemiological studies have suggested a correlation between Vitamin D-deficiency and high blood pressure. Our recent studies demonstrate that Vitamin D is a potent endocrine suppressor of renin biosynthesis to regulate the RAS. Mice lacking the Vitamin D receptor (VDR) have elevated production of renin and angiotensin (Ang) II, leading to hypertension, cardiac hypertrophy and increased water intake. These abnormalities can be prevented by treatment with an ACE inhibitor or AT(1) receptor antagonist. Vitamin D repression of renin expression is independent of calcium metabolism, the volume- and salt-sensing mechanisms and the Ang II feedback regulation. In normal mice, Vitamin D-deficiency stimulates renin expression, whereas injection of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] reduces renin synthesis. In cell cultures, 1,25(OH)(2)D(3) directly suppresses renin gene transcription by a VDR-dependent mechanism. Furthermore, we have found that Gemini compounds have more potent renin-suppressing activity than 1,25(OH)(2)D(3). Collectively, our studies reveal a critical role of the Vitamin D endocrine system in the regulation of blood pressure and volume homeostasis, and suggest that low calcemic Vitamin D analogs may potentially be developed into a new class of anti-hypertensive agents to control renin production and blood pressure.
Li
Yan Chun
YC
Department of Medicine, University of Chicago, MC 4076, 5841 S. Maryland Avenue, Chicago, IL 60637, USA. cyan@medicine.bsd.uchicago.edu
Qiao
Guilin
G
Uskokovic
Milan
M
Xiang
Wei
W
Zheng
Wei
W
Kong
Juan
J
D001794:Blood Pressure / Q000502:physiology*; D006801:Humans; D006973:Hypertension / Q000150:complications; D012084:Renin-Angiotensin System / Q000502:physiology*; D014807:Vitamin D / Q000008:administration & dosage / Q000502:physiology*; D014808:Vitamin D Deficiency / Q000150:complications
D014807:Vitamin D