Increased adiposity does not exacerbate impaired vasodilation in rats exposed to eucapnic intermittent hypoxia

Respiration. 2011;81(1):47-56. doi: 10.1159/000320322. Epub 2010 Aug 20.

Abstract

Background: Although there often is a clinical co-incidence of increased adiposity and obstructive sleep apnea, each factor is independently associated with elevated oxidative stress.

Objective: We hypothesized that overweight rats exposed to simulated sleep apnea would develop exacerbated oxidative stress leading to impaired endothelium-dependent vasodilation.

Methods: Rats were fed either a chow or high-fat diet (HFD; 60% kcal from fat) for 6 weeks. During the final 14 days of each diet, animals were exposed to either air or eucapnic intermittent hypoxia (E-IH) to simulate sleep apnea.

Results: Rats exposed to either E-IH or HFD alone showed increases of 161 and 176%, respectively, in oxidative stress (measured as thiobarbituric acid-reactive substances) compared to chow + air controls. However, oxidative stress was lower following combined HFD + E-IH treatment (132% of chow + air controls) compared to each individual treatment. All three treatment groups, chow + E-IH, HFD + air and HFD + E-IH, had increased blood pressure (144.5 ± 4.4, 148.2 ± 5.6, and 136.2 ± 2.0 mm Hg, respectively, vs. chow + air: 123 ± 2.0 mm Hg) and attenuated acetylcholine (ACh)-mediated vasodilation (78.3, 72.7, and 78.2% of the chow + air response at the highest dose of ACh) compared to chow + air controls. Combined HFD and E-IH treatment did not further impair vasodilation compared to chow + E-IH alone. Vasodilatory responses were normalized by the antioxidant EUK-134 in each treatment group.

Conclusions: Increased adiposity and simulated sleep apnea impair endothelium- dependent vasodilation through enhanced generation of reactive oxygen species (ROS). However, the combined treatment does not exacerbate either ROS generation or vascular dysfunction observed with HFD or E-IH alone.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / metabolism
  • Acetylcholine / pharmacology
  • Adipose Tissue / metabolism*
  • Animals
  • Blood Pressure / drug effects*
  • Dietary Fats / administration & dosage
  • Dietary Fats / adverse effects
  • Dietary Fats / metabolism
  • Disease Models, Animal
  • Humans
  • Male
  • Organometallic Compounds / metabolism
  • Overweight / metabolism
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Sprague-Dawley*
  • Reactive Oxygen Species / adverse effects
  • Reactive Oxygen Species / metabolism
  • Salicylates / metabolism
  • Sleep Apnea, Obstructive* / chemically induced
  • Sleep Apnea, Obstructive* / metabolism
  • Vasodilation / drug effects*

Substances

  • Dietary Fats
  • EUK-134
  • Organometallic Compounds
  • Reactive Oxygen Species
  • Salicylates
  • Acetylcholine