Vitamin D Deficiency and Gender Alter Vasoconstrictor and Vasodilator Reactivity in Rat Carotid Artery.

Miklós Sipos,Eszter Mária Horváth,Réka Kollarics,Péter Magyar,Hicham Dalloul,Marianna Török,György L Nádasy,Mária Szekeres,Leila Hadjadj,Nándor Ács,Dóra Gerszi,Bálint Bányai,Réka Eszter Sziva,Szabolcs Várbíró

doi:10.3390/ijms22158029

Miklós Sipos, Eszter Mária Horváth + Show 12 more

Open Access

https://doi.org/10.3390/ijms22158029

Copy DOI

Abstract

The vitamin-D-sensitivity of the cardiovascular system may show gender differences. The prevalence of vitamin D (VD) deficiency (VDD) is high, and it alters cardiovascular function and increases the risk of stroke. Our aim was to investigate the vascular reactivity and histological changes of isolated carotid artery of female and male rats in response to different VD supplies. A total of 48 male and female Wistar rats were divided into four groups: female VD supplemented, female VDD, male VD supplemented, male VDD. The vascular function of isolated carotid artery segments was examined by wire myography. Both vitamin D deficiency and male gender resulted in increased phenylephrine-induced contraction. Acetylcholine-induced relaxation decreased in male rats independently from VD status. Inhibition of prostanoid signaling by indomethacin reduced contraction in females, but increased relaxation ability in male rats. Functional changes were accompanied by VDD and gender-specific histological alterations. Elastic fiber density was significantly decreased by VDD in female rats, but not in males. Smooth muscle actin and endothelial nitric oxide synthase levels were significantly lowered, but the thromboxane receptor was elevated in VDD males. Decreased nitrative stress was detected in both male groups independently from VD supply. The observed interactions between vitamin D deficiency and sex may play a role in the gender difference of cardiovascular risk.

Highlights

IntroductionThe role of vitamin D in cardio- and cerebrovascular health is not clear, disturbances of vitamin D homeostasis—mainly lower vitamin D levels
Gender-specific difference was observed in the phenylephrine-induced contraction at 10−6 mol/L phenylephrine concentration and male gender was associated with more pronounced contraction independently from vitamin D status
The main findings of the present study were the following: (i) the carotid artery, which has a primary role in cerebral blood flow and systemic blood pressure regulation, shows gender differences in its reaction to both vasoconstrictor and vasodilator agents; (ii) vitamin D deficiency causes vascular injury in both sexes; and (iii) gender differences can be observed in the pathomechanism of vascular injury caused by vitamin D deficiency

Summary

Introduction

The role of vitamin D in cardio- and cerebrovascular health is not clear, disturbances of vitamin D homeostasis—mainly lower vitamin D levels Vitamin D deficiency is a potential risk factor for several cardio-cerebrovascular diseases and events, including stroke [5]. Impaired vitamin D signaling in functionally inactive vitamin D receptor mutant male mice caused compromised cerebrovascular adaptation to unilateral carotid artery occlusion [6]. Four-week-long vitamin D deficient and vitamin D toxic (25(OH)D > 200 ng/mL or > 500 nmol/L [2]) diets resulted in significantly decreased carotid artery diameter and significantly enhanced wall thickness in male rats [7]. Patients with ischemic stroke had significantly lower 25(OH)D levels than control ones and, according to multiple logistic regression, vitamin D considered as a significant predictor in stroke patients and vitamin D deficiency is associated with ischemic stroke [8].

Objectives

Methods

Results

Discussion

Conclusion