Vitamin D deficiency attenuates endothelial function by reducing antioxidant activity and vascular eNOS expression in the rat microcirculation

Microvasc Res. 2021 Nov:138:104227. doi: 10.1016/j.mvr.2021.104227. Epub 2021 Jul 27.

Abstract

This study examined the effects of vitamin D deficiency on vascular function and tissue oxidative status in the microcirculation; and whether or not these effects can be ameliorated with calcitriol, the active vitamin D metabolite. Three groups (n = 10 each) of male Sprague Dawley rats were fed for 10 weeks with control diet (CR), vitamin D-deficient diet without (DR), or with oral calcitriol supplementation (0.15 μg/kg) for the last four weeks (DSR). After 10 weeks, rats were sacrificed; mesenteric arterial rings were studied using wire myograph. Oxidative stress biomarkers malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity were measured in the mesenteric arterial tissue. Vascular protein expression of endothelial nitric oxide synthase (eNOS) was determined by Western blotting. Acetylcholine-induced endothelium-dependent relaxation of DR was lower than CR. eNOS expression and SOD activity were lower in mesenteric arterial tissue of DR compared to CR. Calcitriol supplementation to DSR did not ameliorate the above parameters; in fact, augmented endothelium-dependent contraction was observed. Serum calcium was higher in DSR compared to CR and DR. In conclusion, vitamin D deficiency impaired microvascular vasodilation, associated with eNOS downregulation and reduced antioxidant activity. Calcitriol supplementation to vitamin D-deficient rats at the dosage used augmented endothelium-dependent contraction, possibly due to hypercalcaemia.

Keywords: Calcitriol; Endothelial nitric oxide synthase; Microvascular endothelial function; Oxidative stress; Vitamin D deficiency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / metabolism*
  • Calcitriol / pharmacology
  • Calcium / blood
  • Disease Models, Animal
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / enzymology*
  • Endothelium, Vascular / physiopathology
  • Male
  • Malondialdehyde / metabolism
  • Microcirculation* / drug effects
  • Microvessels / drug effects
  • Microvessels / enzymology*
  • Microvessels / physiopathology
  • Nitric Oxide Synthase Type III / metabolism*
  • Oxidative Stress* / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Superoxide Dismutase / metabolism
  • Vasodilation* / drug effects
  • Vitamin D Deficiency / drug therapy
  • Vitamin D Deficiency / enzymology*
  • Vitamin D Deficiency / physiopathology
  • Vitamins / pharmacology

Substances

  • Antioxidants
  • Vitamins
  • Malondialdehyde
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat
  • Superoxide Dismutase
  • Calcitriol
  • Calcium