AORTIC REACTIVITY IN VITAMIN D DEFICIENCY IN A RAT MODEL OF POLYCYSTIC OVARY SYNDROME

Abstract

Objective: Polycystic ovary syndrome (PCOS) and vitamin D deficiency are associated with elevated cardiovascular risk, whereas vitamin D deficiency is a common comorbidity in PCOS that may contribute to the pathogenesis and complications of the disease. Our aim was to investigate the role of vitamin D status on the aortic function of hyperandrogenic female rats showing the symptoms of PCOS. Design and method: Female Wistar rats received an 8-week-long transdermal Androgel treatment to induce hyperandrogenism, another group remained untreated. Half of each group was fed with vitamin D reduced rat chow, while the other half received normal chow with further supplementation of vitamin D. Norepinephrine-induced contraction, acetylcholine, insulin, and estrogen-induced relaxation of thoracic aortae was examined by wire myography. Elastic fiber density was evaluated on resorcin-fuchsin stained tissue sections. Estrogen receptor alpha, endothelial nitric oxide synthase (eNOS), and cyclooxygenase 2 (COX-2) density and protein tyrosine nitration (NT) was measured by immunohistochemistry. Results: There was no difference in the norepinephrine-induced contraction of the aortas between experimental groups. Reduced acetylcholine-, insulin- and estrogen-evoked relaxation was observed in vitamin D deficient groups. A lower level of resorcin-fuchsin staining and elevated 3- nitrotyrosine immunostaining was observed in non-hyperandrogenic vitamin D deficient rats. eNOS staining intensity was reduced by vitamin D deficiency, while COX-2 density was increased by testosterone treatment. Estrogen receptor alpha density was increased by testosterone treatment but reduced by vitamin D deficiency. Conclusions: We demonstrated an early endothelial dysfunction in a rat model of vitamin D deficient polycystic ovary syndrome. Vitamin D supplementation could prevent vascular damage. On the other hand, vitamin D deficiency itself led to decreased endothelium-dependent relaxation and increased nitrative stress. Vitamin D deficiency also led to decreased estrogen receptor alpha and eNOS density independently from hyperandrogenism. Vitamin D deficiency found in approximately 80% of PCOS women may have a significant role in the development of vascular dysfunction and may contribute to their increased cardiovascular risk.