title: Arteriolar insulin resistance in a rat model of polycystic ovary syndrome.
abstract: OBJECTIVE
  To investigate the vascular dysfunction caused by insulin resistance in polycystic ovary syndrome (PCOS) and the effectiveness of vitamin D in an animal model.
  
  
  METHODS
  Controlled experimental animal study.
  
  
  METHODS
  Animal laboratory at a university research institute.
  
  
  METHODS
  Thirty female Wistar rats.
  
  
  METHODS
  Rats were divided into groups at age 21-28 weeks. Twenty of them were subjected to dihydrotestosterone (DHT) treatment (83 μg/d); ten of them also received parallel vitamin D treatment (120 ng/100 g/wk). Oral glucose tolerance tests with insulin level measurements were performed. Gracilis arterioles were tested for their contractility as well as their nitric oxide (NO)-dependent and insulin-induced dilation using pressure arteriography.
  
  
  METHODS
  Several physiologic parameters, glucose metabolism, and pressure arteriography.
  
  
  RESULTS
  DHT treatment increased the passive diameter of resistance arterioles, lowered norepinephrine-induced contraction (30.1 ± 4.7% vs. 8.7 ± 3.6%) and reduced acetylcholine-induced (122.0 ± 2.9% vs. 48.0 ± 1.4%) and insulin-induced (at 30 mU/mL: 21.7 ± 5.3 vs. 9.8 ± 5.6%) dilation. Vitamin D treatment restored insulin relaxation and norepinephrine-induced contractility; in contrast, it failed to alter NO-dependent relaxation.
  
  
  CONCLUSIONS
  In DHT-treated rats, in addition to metabolically proven insulin resistance, decreased insulin-induced vasorelaxation was observed and was improved by vitamin D treatment without affecting NO-dependent relaxation. The reduction in insulin-induced dilation of arterioles is an important as yet undescribed pathway of vascular damage in PCOS and might explain the clinical effectiveness of vitamin D treatment.
authors.affiliation: Second Department of Obstetrics and Gynecology, Semmelweis University Budapest, Budapest, Hungary. saralevente@gmail.com
authors.forename: Levente
authors.initials: L
authors.lastname: Sara
authors.forename: Peter
authors.initials: P
authors.lastname: Antal
authors.forename: Gabriella
authors.initials: G
authors.lastname: Masszi
authors.forename: Anna
authors.initials: A
authors.lastname: Buday
authors.forename: Eszter M
authors.initials: EM
authors.lastname: Horvath
authors.forename: Peter
authors.initials: P
authors.lastname: Hamar
authors.forename: Emil
authors.initials: E
authors.lastname: Monos
authors.forename: Gyorgy L
authors.initials: GL
authors.lastname: Nadasy
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Varbiro
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D001786:Blood Glucose / Q000378:metabolism; D002762:Cholecalciferol / Q000494:pharmacology; D013196:Dihydrotestosterone; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D018482:Muscle, Skeletal / Q000098:blood supply*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D004791:Enzyme Inhibitors; D007328:Insulin; D014665:Vasodilator Agents; D013196:Dihydrotestosterone; D002762:Cholecalciferol; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester