title: Endothelial relaxation mechanisms and nitrative stress are partly restored by Vitamin D3 therapy in a rat model of polycystic ovary syndrome.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Female Wistar rats weighing 100-140g 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Nitrative stress may play a role in the pathogenesis of PCOS and in the development of the therapeutic effect of vitamin D3.
authors.affiliation: Department of Cardiology, Bajcsy-Zsilinszky Hospital, Budapest, Hungary.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Masszi
authors.forename: Rita
authors.initials: R
authors.lastname: Benko
authors.forename: Noemi
authors.initials: N
authors.lastname: Csibi
authors.forename: Eszter M
authors.initials: EM
authors.lastname: Horvath
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Tokes
authors.forename: Agnes
authors.initials: A
authors.lastname: Novak
authors.forename: Nora Judit
authors.initials: NJ
authors.lastname: Beres
authors.forename: Robert
authors.initials: R
authors.lastname: Tarszabo
authors.forename: Anna
authors.initials: A
authors.lastname: Buday
authors.forename: Csaba
authors.initials: C
authors.lastname: Repas
authors.forename: Gabor
authors.initials: G
authors.lastname: Bekesi
authors.forename: Attila
authors.initials: A
authors.lastname: Patocs
authors.forename: Gyorgy L
authors.initials: GL
authors.lastname: Nadasy
authors.forename: Peter
authors.initials: P
authors.lastname: Hamar
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Benyo
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Varbiro
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002762:Cholecalciferol / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006801:Humans; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010053:Ovary / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects*; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*; D014815:Vitamins / Q000494:pharmacology*
chemical_list: D014815:Vitamins; D002762:Cholecalciferol; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat
keywords: COX; Endothelial function; NOS; Nitrative stress; Polycystic ovary syndrome