Dr. Ron’s Research Review – July 8, 2015

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This week’s research review focuses on vitamin D and ACE and hypertension.

A study published in the Journal of Clinical Investigation showed that vitamin D3 is negative endocrine regulator of the renin-angiotensin system. (Li et al., 2002)

Renin expression and plasma angiotensin II production were increased several-fold 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 were still intact. 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.

In normal mice, Vitamin D-deficiency stimulates renin expression, whereas injection of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] reduces renin synthesis. In cell cultures, 1,25(OH)2D3 directly suppresses renin gene transcription by a VDR-dependent mechanism. (Li et al., 2004)

Dr. Ron


 

Articles

1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system.
(Li et al., 2002) Download
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.

Vitamin D regulation of the renin-angiotensin system.
(Li, 2003) Download
The renin-angiotensin system (RAS) plays a central role in the regulation of blood pressure, electrolyte, and volume homeostasis. Epidemiological and clinical studies have long suggested an association of inadequate sunlight exposure or low serum 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] levels with high blood pressure and/or high plasma renin activity, but the mechanism is not understood. Our recent discovery that 1,25(OH)(2)D(3) functions as a potent negative endocrine regulator of renin gene expression provides some insights into the mechanism. The concept of vitamin D regulation of blood pressure through the RAS opens a new avenue to our understanding of the physiological functions of the vitamin D endocrine system, and provides a basis for exploring the potential use of vitamin D analogues in prevention and treatment of hypertension.


 

Vitamin D regulation of the renin-angiotensin system.
(Li et al., 2004) Download
The renin-angiotensin system (RAS) plays a central role in the regulation of blood pressure, electrolyte, and volume homeostasis. Epidemiological and clinical studies have long suggested an association of inadequate sunlight exposure or low serum 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] levels with high blood pressure and/or high plasma renin activity, but the mechanism is not understood. Our recent discovery that 1,25(OH)(2)D(3) functions as a potent negative endocrine regulator of renin gene expression provides some insights into the mechanism. The concept of vitamin D regulation of blood pressure through the RAS opens a new avenue to our understanding of the physiological functions of the vitamin D endocrine system, and provides a basis for exploring the potential use of vitamin D analogues in prevention and treatment of hypertension.

 

 

References

Li, YC, et al. (2002), ‘1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system.’, J Clin Invest, 110 (2), 229-38. PubMedID: 12122115
Li, YC (2003), ‘Vitamin D regulation of the renin-angiotensin system.’, J Cell Biochem, 88 (2), 327-31. PubMedID: 12520534
Li, YC, et al. (2004), ‘Vitamin D: a negative endocrine regulator of the renin-angiotensin system and blood pressure.’, J Steroid Biochem Mol Biol, 89-90 (1-5), 387-92. PubMedID: 15225806