Reactive oxygen species modulate coronary wall shear stress and endothelial function during hyperglycemia

被引:51
|
作者
Gross, ER
LaDisa, JF
Weihrauch, D
Olson, LE
Kress, TT
Hettrick, DA
Pagel, PS
Warltier, DC
Kersten, JR
机构
[1] Med Coll Wisconsin, Dept Anesthesiol, Milwaukee, WI 53226 USA
[2] Med Coll Wisconsin, Dept Med, Div Cardiovasc Dis, Milwaukee, WI 53226 USA
[3] Med Coll Wisconsin, Dept Pharmacol & Toxicol, Milwaukee, WI 53226 USA
[4] Clement J Zablocki Dept Vet Affairs Med Ctr, Milwaukee, WI 53226 USA
[5] Marquette Univ, Dept Biomed Engn, Milwaukee, WI 53233 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 2003年 / 284卷 / 05期
关键词
coronary artery disease; diabetes; oscillatory shear stress; oxidant stress;
D O I
10.1152/ajpheart.01013.2002
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:H1552 / H1559
页数:8
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