Vol. 284, Issue 5, H1552-H1559, May 2003
Reactive oxygen species modulate coronary wall shear stress
and endothelial function during hyperglycemia
Eric R.
Gross*,1,2,3,
John F.
LaDisa Jr.*,1,3,
Dorothee
Weihrauch1,
Lars E.
Olson3,
Tobias T.
Kress1,
Douglas A.
Hettrick1,3,
Paul
S.
Pagel1,3,
David C.
Warltier1,2,3,4, and
Judy R.
Kersten1,2
Departments of 1 Anesthesiology,
4 Medicine (Division of Cardiovascular Diseases) and
2 Pharmacology and Toxicology, Medical College of
Wisconsin and Clement J. Zablocki Department of Veterans Affairs
Medical Center, Milwaukee 53226; and 3 Department of
Biomedical Engineering, Marquette University, Milwaukee, Wisconsin
53233
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.
coronary artery disease; diabetes; oscillatory shear stress; oxidant stress
*
E. R. Gross and J. F. LaDisa, Jr. contributed
equally to this work.