Increased adiposity does not exacerbate impaired vasodilation in rats exposed to eucapnic intermittent hypoxia.
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.
Sweazea
Karen L
KL
Vascular Physiology Group, Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, N. Mex., USA. Karen.Sweazea@asu.edu
Kanagy
Nancy L
NL
Walker
Benjimen R
BR
D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D009942:Organometallic Compounds / Q000378:metabolism; D050177:Overweight / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000009:adverse effects / Q000378:metabolism; D012459:Salicylates / Q000378:metabolism; D020181:Sleep Apnea, Obstructive / Q000139:chemically induced / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*
D004041:Dietary Fats; C433928:EUK-134; D009942:Organometallic Compounds; D017382:Reactive Oxygen Species; D012459:Salicylates; D000109:Acetylcholine