Vitamin D Deficiency Reduces Vascular Reactivity of Coronary Arterioles in Male Rats

Curr Issues Mol Biol. 2021 May 7;43(1):79-92. doi: 10.3390/cimb43010007.

Abstract

Background: Vitamin D deficiency (VDD) may be considered an independent cardiovascular (CV) risk factor, and it is well known that CV risk is higher in males. Our goal was to investigate the pharmacological reactivity and receptor expression of intramural coronary artery segments of male rats in cases of different vitamin D supply.

Methods: Four-week-old male Wistar rats were divided into a control group (n = 11) with optimal vitamin D supply (300 IU/kgbw/day) and a VDD group (n = 11, <0.5 IU/kgbw/day). After 8 weeks of treatment, intramural coronary artery segments were microprepared, their pharmacological reactivity was examined by in vitro microangiometry, and their receptor expression was investigated by immunohistochemistry.

Results: Thromboxane A2 (TXA2)-agonist induced reduced vasoconstriction, testosterone (T) and 17-β-estradiol (E2) relaxations were significantly decreased, a significant decrease in thromboxane receptor (TP) expression was shown, and the reduction in estrogen receptor-α (ERα) expression was on the border of significance in the VDD group.

Conclusions: VD-deficient male coronary arteries showed deteriorated pharmacological reactivity to TXA2 and sexual steroids (E2, T). Insufficient vasoconstrictor capacity was accompanied by decreased TP receptor expression, and vasodilator impairments were mainly functional. The decrease in vasoconstrictor and vasodilator responses results in narrowed adaptational range of coronaries, causing inadequate coronary perfusion that might contribute to the increased CV risk in VDD.

Keywords: cardiovascular disease; estradiol; male; pharmacological reactivity; rat model; testosterone; thromboxane; vitamin D deficiency.

MeSH terms

  • Androgens / pharmacology
  • Animals
  • Arterioles / metabolism
  • Arterioles / pathology*
  • Coronary Artery Disease / drug therapy
  • Coronary Artery Disease / etiology
  • Coronary Artery Disease / metabolism
  • Coronary Artery Disease / pathology*
  • Disease Models, Animal
  • Estradiol / pharmacology*
  • Estrogens / pharmacology
  • Male
  • Rats
  • Rats, Wistar
  • Receptors, Thromboxane / metabolism
  • Testosterone / pharmacology*
  • Thromboxane A2 / pharmacology*
  • Vasoconstriction
  • Vitamin D Deficiency / complications*
  • Vitamin D Deficiency / metabolism
  • Vitamin D Deficiency / pathology

Substances

  • Androgens
  • Estrogens
  • Receptors, Thromboxane
  • Testosterone
  • Estradiol
  • Thromboxane A2