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Reactive oxygen species modulate coronary wall shear stress and endothelial function during hyperglycemia. Am J Physiol Heart Circ Physiol 2003 May;284(5):H1552-9

Date

01/25/2003

Pubmed ID

12543642

DOI

10.1152/ajpheart.01013.2002

Abstract

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.

Author List

Gross ER, LaDisa JF Jr, Weihrauch D, Olson LE, Kress TT, Hettrick DA, Pagel PS, Warltier DC, Kersten JR

Authors

John LaDisa PhD Assistant Professor in the Biomedical Engineering department at Marquette University
Paul S. Pagel MD, PhD Professor in the Anesthesiology department at Medical College of Wisconsin
Dorothee Weihrauch DVM, PhD Professor in the Anesthesiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Antioxidants
Coronary Artery Disease
Coronary Vessels
Cyclic N-Oxides
Dogs
Endothelium, Vascular
Female
Glucose
Hyperglycemia
Male
Oxidative Stress
Reactive Oxygen Species
Spin Labels
Stress, Mechanical
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