Administration of exogenous 1,25(OH)2D3 normalizes overactivation of the central renin-angiotensin system in 1α(OH)ase knockout mice.

Abstract

Previously, we reported that active vitamin D deficiency in mice causes secondary hypertension and cardiac dysfunction, but the underlying mechanism remains largely unknown. To clarify whether exogenous active vitamin D rescues hypertension by normalizing the altered central renin-angiotensin system (RAS) via an antioxidative stress mechanism, 1-alpha-hydroxylase [1α(OH)ase] knockout mice [1α(OH)ase(-/-)] and their wild-type littermates were fed a normal diet alone or with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], or a high-calcium, high-phosphorus "rescue" diet with or without antioxidant N-acetyl-l-cysteine (NAC) supplementation for 4 weeks. Compared with their wild-type littermates, 1α(OH)ase(-/-)mice had high mean arterial pressure, increased levels of renin, angiotensin II (Ang II), and Ang II type 1 receptor, and increased malondialdehyde levels, but decreased anti-peroxiredoxin I and IV proteins and the antioxidative genes glutathione reductase (Gsr) and glutathione peroxidase 4 (Gpx4) in the brain samples. Except Ang II type 1 receptor, these pathophysiological changes were rescued by exogenous 1,25(OH)2D3 or NAC plus rescue diet, but not by rescue diet alone. We conclude that 1,25(OH)2D3 normalizes the altered central RAS in 1α(OH)ase(-/-)mice, at least partially, through a central antioxidative mechanism.

• Authors: Wei Zhang, Lulu Chen, Luqing Zhang, Ming Xiao, Jiong Ding, David Goltzman, Dengshun Miao
• Journal: Neuroscience letters (Neurosci Lett) Vol. 588 Pg. 184-9 (Feb 19 2015) ISSN: 1872-7972 [Electronic] Ireland
• PMID: 25576706 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Antioxidants
• Receptor, Angiotensin, Type 1
• Vitamins
• Angiotensin II
• Phosphorus
• Steroid Hydroxylases
• vitamin D 1-alpha hydroxylase
• Renin
• Calcitriol
• Calcium
• Acetylcysteine

Topics

• Acetylcysteine (administration & dosage)
• Angiotensin II (metabolism)
• Animals
• Antioxidants (administration & dosage)
• Blood Pressure (drug effects)
• Brain (drug effects, metabolism)
• Calcitriol (pharmacology)
• Calcium (administration & dosage)
• Diet
• Mice, Knockout
• Oxidative Stress (drug effects)
• Phosphorus (administration & dosage)
• Receptor, Angiotensin, Type 1 (metabolism)
• Renin (metabolism)
• Renin-Angiotensin System (drug effects, physiology)
• Steroid Hydroxylases (genetics)
• Vitamins (pharmacology)