Vitamin D Deficiency Causes Inward Hypertrophic Remodeling and Alters Vascular Reactivity of Rat Cerebral Arterioles

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2018 Feb 7

PMID 29408903

Citations 15

Authors

Eva Pal

Leila Hadjadj

Zoltan Fontanyi

Anna Monori-Kiss

Zsuzsanna Mezei

Norbert Lippai

Attila Magyar

Andrea Heinzlmann

Gellert Karvaly

Emil Monos

Gyorgy Nadasy

Zoltan Benyo

Szabolcs Varbiro

Affiliations

Soon will be listed here.

Abstract

Background And Purpose: 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. The goal of the present work was to examine the effects of VDD on the morphological, biomechanical and functional properties of cerebral arterioles.

Methods: 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.

Conclusions: 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.

Citing Articles

Physiological Evidence and Therapeutic Outcomes of Vitamin D on Cardiovascular Diseases.

Zendehdel A, Shakarami A, Moghadam E Curr Cardiol Rev. 2024; .

PMID: 38243935 PMC: 11071673. DOI: 10.2174/011573403X263417231107110618.

Effects of Gender and Vitamin D on Vascular Reactivity of the Carotid Artery on a Testosterone-Induced PCOS Model.

Suli A, Magyar P, Vezer M, Banyai B, Szekeres M, Sipos M Int J Mol Sci. 2023; 24(23).

PMID: 38068901 PMC: 10706740. DOI: 10.3390/ijms242316577.

Disruption of Vitamin D Signaling Impairs Adaptation of Cerebrocortical Microcirculation to Carotid Artery Occlusion in Hyperandrogenic Female Mice.

Nagy D, Hricisak L, Walford G, Lekai A, Karacsony G, Varbiro S Nutrients. 2023; 15(18).

PMID: 37764653 PMC: 10534509. DOI: 10.3390/nu15183869.

Role of Vitamin D Deficiency in the Pathogenesis of Cardiovascular and Cerebrovascular Diseases.

Pal E, Ungvari Z, Benyo Z, Varbiro S Nutrients. 2023; 15(2).

PMID: 36678205 PMC: 9864832. DOI: 10.3390/nu15020334.

Vitamin-D Deficiency and Supplementation Altered the Network of the Coronary Arteries in a Rodent Model-In Situ Video Microscopic Technique.

Dalloul H, Hainzl T, Monori-Kiss A, Hadjadj L, Nadasy G, Torok M Nutrients. 2022; 14(10).

PMID: 35631182 PMC: 9144105. DOI: 10.3390/nu14102041.

References

Rizzoni D, Porteri E, Castellano M, Bettoni G, Muiesan M, Muiesan P . Vascular hypertrophy and remodeling in secondary hypertension. Hypertension. 1996; 28(5):785-90. DOI: 10.1161/01.hyp.28.5.785. View

Mozos I, Marginean O . Links between Vitamin D Deficiency and Cardiovascular Diseases. Biomed Res Int. 2015; 2015:109275. PMC: 4427096. DOI: 10.1155/2015/109275. View

Rafraf M, Karimi Hasanabad S, Jafarabadi M . Vitamin D status and its relationship with metabolic syndrome risk factors among adolescent girls in Boukan, Iran. Public Health Nutr. 2014; 17(4):803-9. PMC: 10282248. DOI: 10.1017/S1368980013003340. View

Holick M . Vitamin D deficiency. N Engl J Med. 2007; 357(3):266-81. DOI: 10.1056/NEJMra070553. View

Mehta V, Agarwal S . Does Vitamin D Deficiency Lead to Hypertension?. Cureus. 2017; 9(2):e1038. PMC: 5356990. DOI: 10.7759/cureus.1038. View

Izzard A, Rizzoni D, Agabiti-Rosei E, Heagerty A . Small artery structure and hypertension: adaptive changes and target organ damage. J Hypertens. 2005; 23(2):247-50. DOI: 10.1097/00004872-200502000-00002. View

Meems L, Mahmud H, Buikema H, Tost J, Michel S, Takens J . Parental vitamin D deficiency during pregnancy is associated with increased blood pressure in offspring via Panx1 hypermethylation. Am J Physiol Heart Circ Physiol. 2016; 311(6):H1459-H1469. DOI: 10.1152/ajpheart.00141.2016. View

Kojima G, Bell C, Abbott R, Launer L, Chen R, Motonaga H . Low dietary vitamin D predicts 34-year incident stroke: the Honolulu Heart Program. Stroke. 2012; 43(8):2163-7. PMC: 3404239. DOI: 10.1161/STROKEAHA.112.651752. View

Brondum-Jacobsen P, Nordestgaard B, Schnohr P, Benn M . 25-hydroxyvitamin D and symptomatic ischemic stroke: an original study and meta-analysis. Ann Neurol. 2012; 73(1):38-47. DOI: 10.1002/ana.23738. View

10.

Argacha J, Egrise D, Pochet S, Fontaine D, Lefort A, Libert F . Vitamin D deficiency-induced hypertension is associated with vascular oxidative stress and altered heart gene expression. J Cardiovasc Pharmacol. 2011; 58(1):65-71. DOI: 10.1097/FJC.0b013e31821c832f. View

11.

Sun Q, Pan A, Hu F, Manson J, Rexrode K . 25-Hydroxyvitamin D levels and the risk of stroke: a prospective study and meta-analysis. Stroke. 2012; 43(6):1470-7. PMC: 3361562. DOI: 10.1161/STROKEAHA.111.636910. View

12.

Li Y, Qiao G, Uskokovic M, Xiang W, Zheng W, Kong J . Vitamin D: a negative endocrine regulator of the renin-angiotensin system and blood pressure. J Steroid Biochem Mol Biol. 2004; 89-90(1-5):387-92. DOI: 10.1016/j.jsbmb.2004.03.004. View

13.

Sundersingh F, Plum L, Deluca H . Vitamin D deficiency independent of hypocalcemia elevates blood pressure in rats. Biochem Biophys Res Commun. 2015; 461(4):589-91. DOI: 10.1016/j.bbrc.2015.04.069. View

14.

Husain K, Suarez E, Isidro A, Ferder L . Effects of paricalcitol and enalapril on atherosclerotic injury in mouse aortas. Am J Nephrol. 2010; 32(4):296-304. DOI: 10.1159/000319445. View

15.

Feletou M, Cohen R, Vanhoutte P, Verbeuren T . TP receptors and oxidative stress hand in hand from endothelial dysfunction to atherosclerosis. Adv Pharmacol. 2010; 60:85-106. PMC: 3004095. DOI: 10.1016/B978-0-12-385061-4.00004-0. View

16.

Milazzo V, De Metrio M, Cosentino N, Marenzi G, Tremoli E . Vitamin D and acute myocardial infarction. World J Cardiol. 2017; 9(1):14-20. PMC: 5253190. DOI: 10.4330/wjc.v9.i1.14. View

17.

Chung P, Park K, Kim J, Shin D, Park M, Chung Y . 25-hydroxyvitamin D status is associated with chronic cerebral small vessel disease. Stroke. 2014; 46(1):248-51. DOI: 10.1161/STROKEAHA.114.007706. View

18.

Laursen J, Somers M, Kurz S, McCann L, Warnholtz A, Freeman B . Endothelial regulation of vasomotion in apoE-deficient mice: implications for interactions between peroxynitrite and tetrahydrobiopterin. Circulation. 2001; 103(9):1282-8. DOI: 10.1161/01.cir.103.9.1282. View

19.

Prabhakar P, Chandra S, Supriya M, Issac T, Prasad C, Christopher R . Vitamin D status and vascular dementia due to cerebral small vessel disease in the elderly Asian Indian population. J Neurol Sci. 2015; 359(1-2):108-11. DOI: 10.1016/j.jns.2015.10.050. View

20.

Lehoux S, Castier Y, Tedgui A . Molecular mechanisms of the vascular responses to haemodynamic forces. J Intern Med. 2006; 259(4):381-92. DOI: 10.1111/j.1365-2796.2006.01624.x. View