Reactive Oxygen Species Modulate Coronary Wall Shear Stress and Endothelial Function During Hyperglycemia

Authors

Eric R. Gross, Medical College of WisconsinFollow
John F. LaDisa, Marquette UniversityFollow
Dorothee Weihrauch, Medical College of Wisconsin
Lars E. Olson, Marquette UniversityFollow
Tobias T. Kress, Medical College of Wisconsin
Douglas Anthony Hettrick, Marquette UniversityFollow
Paul S. Pagel, Marquette UniversityFollow
David C. Warltier, Marquette UniversityFollow
Judy R. Kersten, Medical College of Wisconsin

Document Type

Article

Language

eng

Format of Original

8 p.

Publication Date

5-2003

Publisher

American Physiological Society

Source Publication

American Journal of Physiology - Heart and Circulatory Physiology

Source ISSN

0363-6135

Original Item ID

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.

Comments

Accepted version. American Journal of Physiology - Heart and Circulatory Physiology, Vol. 284, No. 5 (May 2003): H1552-H1559. DOI. © American Physiological Society. Used with permission.

Recommended Citation

Gross, Eric R.; LaDisa, John F.; Weihrauch, Dorothee; Olson, Lars E.; Kress, Tobias T.; Hettrick, Douglas Anthony; Pagel, Paul S.; Warltier, David C.; and Kersten, Judy R., "Reactive Oxygen Species Modulate Coronary Wall Shear Stress and Endothelial Function During Hyperglycemia" (2003). Biomedical Engineering Faculty Research and Publications. 219.
https://epublications.marquette.edu/bioengin_fac/219