The Effects of Modulating Endothelial Nitric Oxide Synthese (eNOS) Activity and Coupling in Extracorporeal Shock Wave Lithotripsy (ESWL)Research Day
Start Date1-5-2013 2:00 PM
End Date1-5-2013 4:00 PM
DescriptionIntroduction: ESWL is a clinical therapy to break down kidney and uretal stones into smaller fragments that are more easily eliminated through the urinary tract. High-energy shock waves are focused on the stone to cause shear stress and cavitation bubbles which synergistically ablate the stones. While ESWL is the preferred treatment for kidney stones over invasive surgeries, the repetitive shock waves necessary to break up the stones may also cause damage to the renal vasculature endothelium and that can lead to chronic hypertension . Previous studies have found that ESWL can cause endothelial dysfunction which is characterized decreased nitric oxide (NO) bioavailability and increased production of reactive oxygen species (ROS) such as superoxide (O2-) . Normally, endothelial nitric oxide synthase (eNOS) is in a coupled state which forms NO in the presence of essential cofactor tetrahydrobiopterin (BH4) and molecular oxygen. Oxidative stress, such as that caused by ESWL-induced ROS, can cause BH4 to be oxidized to dihydrobiopterin (BH2). When the BH2:BH4 ratio is increased, eNOS becomes uncoupled and produces O2- instead of NO [2, 3] (Figure 1). O2- is short-lived and converted to hydrogen peroxide (H2O2) in blood by superoxide dismutase. Protein kinase C epsilon (PKCε) has previously been found to regulate eNOS activity via phosphorylation at serine-1177. Cell-permeable PKCε peptide activator (PKCε+) increases eNOS activity while PKCε inhibitor (PKCε-) reduces eNOS activity . Using a combination of eNOS cofactors BH4 or BH2 with eNOS activity regulators PKCε+ or PKCε-, we can explore the role of modulating eNOS to reduce oxidative stress and endothelial dysfunction caused by ESWL.
Citation InformationAlexandra Lopez, Qian Chen, Brittany L. Deiling, Edward S. Iames, et al.. "The Effects of Modulating Endothelial Nitric Oxide Synthese (eNOS) Activity and Coupling in Extracorporeal Shock Wave Lithotripsy (ESWL)" (2013)
Available at: http://works.bepress.com/qian_chen/25/