Imbalance of Pro- and Anti-Angiogenic Factors Due to Maternal Vitamin D Deficiency Causes Renal Microvasculature Alterations Affecting the Adult Kidney Function

Abstract

Vitamin D (Vit.D) is involved in cellular proliferation and differentiation and regulation of the renin gene, which are important aspects of nephrogenesis and quiescence of renal health in adulthood. This study evaluated the angiogenic mechanisms involved in long term renal disturbances induced by Vit.D deficiency persistent in adulthood in rats. First-generation male Hannover offspring from mothers fed either a control diet (control group, CG) or Vit.D-deficient diet (Vit.D- group) were evaluated. Systolic blood pressure (SBP) was measured monthly during the first 6 months after birth, and blood and urine samples were collected to evaluate renal function. Nitric oxide (NO), angiotensin II (ANGII), parathyroid hormone (PTH), calcium, and Vit.D were measured. The kidneys were then removed for morphometric, NO, immunohistochemical, and Western blot studies. We evaluated the expression of vascular growth factor (VEGF) and angiopoietins 1 and 2 and their receptors since this intrinsic renal axis is responsible for endothelial quiescence. Compared to CG, the Vit.D- group presented higher SBP, ANG II plasma levels, renin expression, and AT1 receptor expression levels. Capillary rarefaction was observed, as well as an imbalance between pro- and anti-angiogenic factors. Collectively, the present findings support the role of Vit.D for maintaining the integrity of renal microcirculation.