Arteriolar insulin resistance in a rat model of polycystic ovary syndrome

Fertil Steril. 2012 Feb;97(2):462-8. doi: 10.1016/j.fertnstert.2011.11.015. Epub 2011 Dec 10.

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.

Design: Controlled experimental animal study.

Setting: Animal laboratory at a university research institute.

Animal(s): Thirty female Wistar rats.

Intervention(s): 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.

Main outcome measure(s): Several physiologic parameters, glucose metabolism, and pressure arteriography.

Result(s): 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.

Conclusion(s): 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Animals
  • Arterioles / drug effects
  • Arterioles / metabolism
  • Arterioles / physiopathology
  • Blood Glucose / metabolism
  • Cholecalciferol / pharmacology
  • Dihydrotestosterone
  • Disease Models, Animal
  • Enzyme Inhibitors / pharmacology
  • Female
  • Glucose Tolerance Test
  • Insulin / blood
  • Insulin Resistance*
  • Muscle, Skeletal / blood supply*
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / metabolism
  • Polycystic Ovary Syndrome / blood
  • Polycystic Ovary Syndrome / chemically induced
  • Polycystic Ovary Syndrome / drug therapy
  • Polycystic Ovary Syndrome / physiopathology*
  • Rats
  • Rats, Wistar
  • Vasodilation* / drug effects
  • Vasodilator Agents / pharmacology

Substances

  • Blood Glucose
  • Enzyme Inhibitors
  • Insulin
  • Vasodilator Agents
  • Dihydrotestosterone
  • Cholecalciferol
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Acetylcholine
  • NG-Nitroarginine Methyl Ester