| First Author | Zhang W | Year | 2015 |
| Journal | Neurosci Lett | Volume | 588 |
| Pages | 184-9 | PubMed ID | 25576706 |
| Mgi Jnum | J:219738 | Mgi Id | MGI:5629635 |
| Doi | 10.1016/j.neulet.2015.01.013 | Citation | Zhang W, et al. (2015) Administration of exogenous 1,25(OH)2D3 normalizes overactivation of the central renin-angiotensin system in 1alpha(OH)ase knockout mice. Neurosci Lett 588:184-9 |
| abstractText | 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 [1alpha(OH)ase] knockout mice [1alpha(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, 1alpha(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 1alpha(OH)ase(-/-)mice, at least partially, through a central antioxidative mechanism. |
