Effects of Protein Kinase C Selective Beta II Peptide Inhibitor on Real-Time Blood Nitric Oxide and Hydrogen Peroxide Release Under Acute Hyperglycemia

摘要

Vascular endothelial dysfunction is one of the earliest recognizable events under hyperglycemic conditions. It is characterized by decreased endothelium-derived nitric oxide (NO) from endothelial NO synthase (eNOS) and increased oxidative stress, such as superoxide and hydrogen peroxide (H2O2). In a state of hyperglycemia, the enzyme protein kinase C (PKC), especially PKC beta II, becomes stimulated, which activates NADPH oxidase generating superoxide and also inhibits eNOS attenuating NO production. Moreover, superoxide can either directly quench NO to form peroxynitrite (0N00-) or be converted to H2O2 by superoxide dismutase. Both ONOO- and H2O2 can promote eNOS uncoupling to produce superoxide instead of NO. Therefore, more superoxide is generated and less NO is remained available. Thereby, a vicious cycle can propagate causing vascular endothelial damage and if prolonged can ultimately cause organ failure.