Effects of NOX-1 on Real-Time Blood Nitric Oxide and Hydrogen Peroxide in Acute Hyperglycemia
Hyperglycemia has been associated with vascular endothelial dysfunction in part by a reduction in nitric oxide (NO) production and increased oxidative stress (e.g., increased superoxide (SO) and hydrogen peroxide (H2O2). Endothelial-derived NO can be significantly reduced by increased SO/H2O2 in part by the activation of NADPH oxidase during hyperglycemia. Of the 7 NADPH oxidase isoforms, NOX1 is mainly expressed in the vasculature and may play a major role in hyperglycemia induced oxidative stress and vascular endothelial dysfunction. To test this hypothesis, we measured blood NO and H2O2 levels in real time via NO and H2O2 microsensors inserted into femoral veins of rats. Hyperglycemia (e.g., 200 mg/dl) was maintained by infusion i.v. of 30% glucose solution for 3 hours with or without a selective NOX1 inhibitor, ML171. We found that hyperglycemia for 3 hours significantly increased blood H2O2 levels by 1.88±0.4 µM (n=6) compared to the saline infused control (P<0.05, n=2). By contrast, ML171 (1 and 5 µM) reduced hyperglycemia-induced H2O2 levels by 1.36±0.61 µM (n=8) and 4.35±1.02 µM (n=5), respectively, at the end of experiment. Meanwhile, hyperglycemia significantly reduced blood NO levels by 82.48±38.12 nM (n=3) compared to the saline control (P<0.05, n=2). By contrast, ML171 (1 µM) attenuated the hyperglycemia induced decrease in blood NO levels and increased blood NO levels by 71.15±24.00 nM (n=5) at the end of experiment. Our preliminary results indicate that NOX1 activation may contribute to hyperglycemia-induced oxidative stress and NO reduction. Furthermore, inhibition of NOX1 may mitigate the deleterious effects of hyperglycemia.
The FASEB Journal
Mawhinney, Ashley; Bertolet, Michael; Minni, Michael; Barsotti, Robert; Young, Lindon; and Chen, Qian, "Effects of NOX-1 on Real-Time Blood Nitric Oxide and Hydrogen Peroxide in Acute Hyperglycemia" (2016). PCOM Scholarly Papers. 1686.