Éva Pál1, Leila Hadjadj1, Anna Monori-Kiss1, Zoltán Fontányi2, , Zsuzsanna Mezei3, Norbert Lippai4, Attila Magyar5, Andrea Heinzlmann5, Gellért Karvaly6,7, Emil Monos1, György Nádasy3, Szabolcs Várbíró2, Zoltán Benyó1
1Institute of Clinical Experimental Research, Semmelweis University, Budapest, Hungary
22nd Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary
3Department of Physiology, Semmelweis University, Budapest, Hungary
4Department of Pathology, Jász-Nagykun-Szolnok County Hetényi Géza Hospital, Szolnok, Hungary
5Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest, Hungary
6Department of Laboratory Medicine, Semmelweis University, Budapest, Hungary
7Bionics Innovation Center, Budapest, Hungary
Introduction: Vitamin 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.
Aims: The goal of the present work was to examine the effects of VDD on the morphological, biomechanical and functional properties of cerebral arterioles.
Method: Four-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.
Results: VDD 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.
Conclusion: VDD 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.
Doctoral School: Basic and Translational Medicine
Program: The Mechanisms of Normal and Pathologic Functions of the Circulatory System
Supervisor: Zoltán Benyó, Emil Monos
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