Date of Award

8-2012

Degree Type

Thesis

Degree Name

Master of Science in Biomedical Sciences

First Advisor

Qian Chen, PhD, Thesis Advisor

Second Advisor

Farzaneh Daghigh, PhD

Third Advisor

Christopher Scott Little, PhD

Fourth Advisor

Marcus Bell, PhD

Abstract

Vascular endothelial dysfunction is one of the earliest recognizable events under hyperglycemic conditions. It is characterized by decreased endothelium-derived nitric oxide (NO) bioavailability and increased oxidative stress, such as superoxide and hydrogen peroxide (H2O2) overproduction. However, the real-time changes in blood NO and H2O2 levels under acute hyperglycemia have not been evaluated. In this study, acute hyperglycemia (200 mg/dl, 400 mg/dL, and 600 mg/dL) was induced by intravenous infusion of 20%, 30%, and 50% D-glucose respectively for 180 min. Infusion of saline or 30% L-glucose serve as controls. Blood NO or H2O2 levels were measured at real-time by inserting calibrated NO or H2O2 microsensors (100 μm diameter) into each femoral vein, respectively. In the saline group, blood NO levels remained stable and only slightly decreased by 17.61±8.04 nM (n=7) at 180 min compared to baseline. By contrast, hyperglycemia significantly decreased blood NO levels from 100-160 min to the end of the experiment. At 180 min, blood NO levels in 200 mg/dL, 400 mg/dL, and ≥600 mg/dL groups were 71.3±17.9 nM (n=7), 112.15±15.28 nM (n=6), and 105.98±23.45 nM (n=6) lower than that in saline group, respectively (all p2O2 levels, which is not principally due to hyperosmolarity.

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