Reactive oxygen species modulate coronary wall shear stress and endothelial function during hyperglycemia.
Hyperglycemia is associated with generation of reactive oxygen species (ROS), and this action may contribute to accelerated atherogenesis. We tested the hypothesis that hyperglycemia produces alterations in left anterior descending coronary artery (LAD) wall shear stress concomitant with endothelial dysfunction and ROS production in dogs (n = 12) instrumented for measurement of LAD blood flow, velocity, and diameter. Dogs were randomly assigned to receive vehicle (0.9% saline) or the superoxide dismutase mimetic 4- hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (tempol) and were administered intravenous infusions of d-glucose to achieve target blood glucose concentrations of 350 and 600 mg/dl (moderate and severe hyperglycemia, respectively). Endothelial function and ROS generation were assessed by coronary blood flow responses to acetylcholine (10, 30, and 100 ng/kg) and dihydroethidium fluorescence of myocardial biopsies, respectively. Indexes of wall shear stress were calculated with conventional fluid dynamics theory. Hyperglycemia produced dose-related endothelial dysfunction, increases in ROS production, and reductions in oscillatory shear stress that were normalized by tempol. The results suggest a direct association between hyperglycemia-induced ROS production, endothelial dysfunction, and decreases in oscillatory shear stress in vivo.
Gross
Eric R
ER
Department of Anesthesiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
LaDisa
John F
JF
Weihrauch
Dorothee
D
Olson
Lars E
LE
Kress
Tobias T
TT
Hettrick
Douglas A
DA
Pagel
Paul S
PS
Warltier
David C
DC
Kersten
Judy R
JR
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D003324:Coronary Artery Disease / Q000378:metabolism / Q000503:physiopathology; D003331:Coronary Vessels / Q000502:physiology*; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004285:Dogs; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000494:pharmacology; D006943:Hyperglycemia / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013113:Spin Labels; D013314:Stress, Mechanical
D000975:Antioxidants; D003497:Cyclic N-Oxides; D017382:Reactive Oxygen Species; D013113:Spin Labels; D005947:Glucose; C001803:tempol