Vitamin D Deficiency Cause Gender Specific Alterations of Renal Arterial Function in a Rodent Model.

Miklós Sipos,Eszter Soltész-Katona,Szabolcs Várbíró,Bálint Bányai,Eszter Mária Horváth,Anita Süli,Mária Szekeres,Dóra Gerszi,Borbála Péterffy,György L Nádasy,Leila Hadjadj,Réka Eszter Sziva,Judit Kiss,Péter Magyar

doi:10.3390/nu13020704

Abstract

Vitamin D deficiency shows positive correlation to cardiovascular risk, which might be influenced by gender specific features. Our goal was to examine the effect of Vitamin D supplementation and Vitamin D deficiency in male and female rats on an important hypertension target organ, the renal artery. Female and male Wistar rats were fed with Vitamin D reduced chow for eight weeks to induce hypovitaminosis. Another group of animals received normal chow with further supplementation to reach optimal serum vitamin levels. Isolated renal arteries of Vitamin D deficient female rats showed increased phenylephrine-induced contraction. In all experimental groups, both indomethacin and selective cyclooxygenase-2 inhibition (NS398) decreased the phenylephrine-induced contraction. Angiotensin II-induced contraction was pronounced in Vitamin D supplemented males. In both Vitamin D deficient groups, acetylcholine-induced relaxation was impaired. In the female Vitamin D supplemented group NS398, in males the indomethacin caused reduced acetylcholine-induced relaxation. Increased elastic fiber density was observed in Vitamin D deficient females. The intensity of eNOS immunostaining was decreased in Vitamin D deficient females. The density of AT1R staining was the highest in the male Vitamin D deficient group. Although Vitamin D deficiency induced renal vascular dysfunction in both sexes, female rats developed more extensive impairment that was accompanied by enzymatic and structural changes.

Highlights

The clear correlation between low plasma Vitamin D levels, hypertension and adverse cardiovascular events is widely described in the scientific literature, but randomized, controlled clinical studies failed to prove the direct advantageous effects of Vitamin D supplementation in cardiovascular prevention [1]
The 8-week-long Vitamin D supplementation resulted in lower 25-OH-D3 level in male rats compared to females, despite the weight-adjusted dosage
Our results confirm that Vitamin D deficiency increases cardiovascular risk in both sexes

Summary

Introduction

The clear correlation between low plasma Vitamin D levels, hypertension and adverse cardiovascular events is widely described in the scientific literature, but randomized, controlled clinical studies failed to prove the direct advantageous effects of Vitamin D supplementation in cardiovascular prevention [1]. Previous studies described differences in Vitamin D metabolism [3,4] and susceptibility to Vitamin D deficiency of the cardiovascular system in males and females [5]. In our study we analyzed the possible gender differences in the effect of vitamin D deficiency and supplementation on renal arterial function. In the current rodent study, the duration of diet-induced hypovitaminosis and Vitamin D supplementation was 8 weeks that allowed us to observe the early signs of the developing vascular changes [7,8,9]. Our goal was to model the appropriate Vitamin D supplementation and relevant Vitamin D deficiency in male and female rats, and to examine their effect on an important hypertension target organ, the renal artery. Our aim was to detect possible gender differences in Vitamin D dependent vascular changes

Objectives

Methods

Findings

Conclusion