Vitamin D deficiency causes inward hypertrophic remodeling and alters vascular reactivity of rat cerebral arterioles

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.

Vitamin D Deficiency Induces Elevated Oxidative and Biomechanical Damage in Coronary Arterioles in Male Rats

“…Lowered wall stress and reduced elastic modulus of arteriole segments were shown in the coronary artery from vitamin-D-deficient female rats [ 23 ]. Cerebral artery from vitamin-D-deficient male rats had attenuated wall stress [ 19 ]. Decreasing tendency of spontaneous tone of vitamin-D-deficient group was not significant, but moving in this direction may develop into a pre-hypertensive lesion due to long-term vitamin-D-deficient state.…”

“…On the other hand, in case of vitamin-D-dependency, the organ or tissue cannot adapt by receptor-upregulation to the concentration changes, so it will be sensitive and vulnerable to vitamin D deficiency. According to our previous results from animal experiments, small vessels from the heart and brain are vitamin-D-dependent tissues, because in extreme vitamin-D-deficient milieu, they go through major changes [ 18 , 19 , 23 , 37 , 42 ], but these alterations are depending on which region the vessels are originated from. Both vitamin D deficiency and toxicity can induce smaller carotid artery diameter and larger wall thickness in male Wistar rat models within 4 weeks [ 43 ].…”

“…An interesting hypothesis is that the efficacy of vitamin D supply and the severity of vitamin D deficiency may show gender and individual differences. Based on animal studies, it seems that in males, higher exogenous vitamin D intake may be required to reach and maintain the same, optimal target range of vitamin D than in females [ 18 , 19 ]. This observation suggests gender and individual differences in vitamin D synthesis, activation, or metabolism.…”

“…The vitamin-D-deficient animals ( n = 11, “VDD” group) received specific vitamin-D-deficient rat chow containing less than 5 IU/kg vitamin D (EF Rat/mouse VitD-free diet E15312-24, Ssniff Spezialdiäten GmbH, Soest, Germany). Blood sample measurements at termination of study have proven a 5 times reduction in serum 25-hydroxy vitamin D levels in deficient animals [ 19 ].…”

Vitamin D3 affects mitochondrial biogenesis through mitogen‐activated protein kinase in polycystic ovary syndrome mouse model

“…Furthermore, several studies have demonstrated the role of vitamin D3 in improving fertility disorders including polycystic ovarian syndrome, endometriosis, premature ovarian failure, male infertility, and in vitro fertilization techniques (Bakhshalizadeh et al, 2017; Pál et al, 2018). Vitamin D3 can, likewise, stimulate follicular development and improve the symptoms of PCOS (Çelik et al, 2018; Fang et al, 2017; Hadjadj et al, 2018).…”