Abstract

Background and purposeVitamin D deficiency (VDD) is a global health problem, which can lead to several pathophysiological consequences including cardiovascular diseases. Its impact on the cerebrovascular system is not well understood. The goal of the present work was to examine the effects of VDD on the morphological, biomechanical and functional properties of cerebral arterioles.MethodsFour-week-old male Wistar rats (n = 11 per group) were either fed with vitamin D deficient diet or received conventional rat chow with per os vitamin D supplementation. Cardiovascular parameters and hormone levels (testosterone, androstenedione, progesterone and 25-hydroxyvitamin D) were measured during the study. After 8 weeks of treatment anterior cerebral artery segments were prepared and their morphological, biomechanical and functional properties were examined using pressure microangiometry. Resorcin-fuchsin and smooth muscle actin staining were used to detect elastic fiber density and smooth muscle cell counts in the vessel wall, respectively. Sections were immunostained for eNOS and COX-2 as well.ResultsVDD markedly increased the wall thickness, the wall-to-lumen ratio and the wall cross-sectional area of arterioles as well as the number of smooth muscle cells in the tunica media. As a consequence, tangential wall stress was significantly lower in the VDD group. In addition, VDD increased the myogenic as well as the uridine 5’-triphosphate-induced tone and impaired bradykinin-induced relaxation. Decreased eNOS and increased COX-2 expression were also observed in the endothelium of VDD animals.ConclusionsVDD causes inward hypertrophic remodeling due to vascular smooth muscle cell proliferation and enhances the vessel tone probably because of increased vasoconstrictor prostanoid levels in young adult rats. In addition, the decreased eNOS expression results in endothelial dysfunction. These morphological and functional alterations can potentially compromise the cerebral circulation and lead to cerebrovascular disorders in VDD.

Highlights

  • Vitamin D deficiency (VDD) or insufficiency affects 1 billion people from all age groups worldwide

  • Decreased eNOS and increased COX-2 expression were observed in the endothelium of VDD animals

  • Marked changes of morphology and reactivity developed in healthy young adult animals within a relatively short period (8 weeks) of VDD indicating the importance of normal vitamin D (VitD) status for the maintenance of cerebrovascular functions

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Summary

Introduction

Vitamin D deficiency (VDD) or insufficiency affects 1 billion people from all age groups worldwide. In addition to its well-characterized roles in calcium and phosphate homeostasis as well as in bone metabolism, 1,25-dihydroxyvitamin D—the active metabolite of vitamin D (VitD)—has numerous biological actions [1]. Diabetes mellitus and metabolic syndrome are linked to VDD, as 1,25-dihydroxyvitamin D improves β-cell function and insulin sensitivity [3]. There is a growing body of evidence linking VDD to cardiovascular diseases including hypertension, atherosclerosis and coronary artery disease. A direct impact of VDD on endothelial dysfunction, arterial stiffness and vascular inflammation was reported [2, 4, 5]. Vitamin D deficiency (VDD) is a global health problem, which can lead to several pathophysiological consequences including cardiovascular diseases. The goal of the present work was to examine the effects of VDD on the morphological, biomechanical and functional properties of cerebral arterioles.

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