Active Vitamin D Corrects Cerebrovascular Dysfunction and Aberrant Vasopressin Expression in the Hypertension Phenotype of 1α-Hydroxylase Knockout Mice

Abstract

Vitamin D has a protective effect on the brain under hypertensive conditions. Studies have shown that 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) can negatively regulate hypertension and central renin-angiotensin system activation through a central anti-oxidative mechanism in 1α-hydroxylase knockout mice. To confirm whether endogenous or exogenous 1,25(OH)₂D₃ deficiency or supplementation alters cerebrovascular function and vasopressin expression through anti-oxidation, researchers provided 1α(OH)ase^−/− mice and their wild-type littermates with regular diet, a high-calcium, high-phosphorus rescue diet with N-acetyl-L-cysteine supplementation, or 1,25(OH)₂D₃ subcutaneous injection. The results showed that the hypertension phenotype was present in the 1α(OH)ase^−/− mice, with upregulated vasopressin expression and increased brain/blood oxidative stress. These pathologic changes were corrected by 1,25(OH)₂D₃ or N-acetyl-L-cysteine plus rescue diet. The findings suggest that 1,25(OH)₂D₃ may be a promising protective intervention to reduce brain impairment induced by oxidative stress in the hypertension phenotype of 1α(OH)ase^−/− mice.