Endothelial relaxation mechanisms and nitrative stress are partly restored by Vitamin D₃ therapy in a rat model of polycystic ovary syndrome

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• 作者：Gabriella Masszi ; Rita Benko ; Noemi Csibi ; Eszter M. Horvath ; Anna-Maria Tokes ; Agnes Novak ; Nora Judit Beres ; Robert Tarszabo ; Anna Buday ; Csaba Repas ; Gabor Bekesi ; Attila Patocs ; Gyorgy L. Nadasy ; Peter Hamar ; Zoltan Benyo ; Szabolcs Varbiro
• 关键词：Polycystic ovary syndrome ; Nitrative stress ; Endothelial function ; NOS ; COX
• 刊名：Life Sciences
• 出版年：2013
• 出版时间：6 August, 2013
• 年：2013
• 卷：93
• 期：4
• 页码：133-138
• 全文大小：1101 K

文摘

Aims

In polycystic ovary syndrome (PCOS), metabolic and cardiovascular dysfunction is related to hyperandrogenic status and insulin resistance, however, Vitamin D3 has a beneficial effect partly due to its anti-oxidant capacity. Nitrative stress is a major factor in the development of cardiovascular dysfunction and insulin resistance in various diseases. Our aim was to determine the effects of vitamin D3 in a rat model of PCOS, particularly the pathogenic role of nitrative stress.

Main methods

Female Wistar rats weighing 100-140 g were administered vehicle (C), dihydrotestosterone (DHT) or dihydrotestosterone plus vitamin D3 (DHT + D) (n = 10 per group). On the 10th week, acetylcholine (Ach) induced relaxation ability of the isolated thoracic aorta rings was determined. In order to examine the possible role of endothelial nitric oxide synthase (eNOS) and cyclooxygenase-2 (COX-2) pathways in the impaired endothelial function, immunohistochemical labeling of aortas with anti-eNOS and anti-COX-2 antibodies was performed. Leukocyte smears, aorta and ovary tissue sections were also immunostained with anti-nitrotyrosine antibody to determine nitrative stress.

Key findings

Relaxation ability of aorta was reduced in group DHT, and vitamin D3 partly restored Ach induced relaxation. eNOS labeling was significantly lower in DHT rats compared to the other two groups, however COX-2 staining showed an increment. Nitrative stress showed a significant increase in response to dihydrotestosterone, while vitamin D3 treatment, in case of the ovaries, was able to reverse this effect.

Significance

Nitrative stress may play a role in the pathogenesis of PCOS and in the development of the therapeutic effect of vitamin D3.