Date of Award


Degree Type


Degree Name

Master of Science (MS)

First Advisor

Lindon Young, PhD

Second Advisor

Qian Chen, PhD

Third Advisor

Charlotte Greene, PhD


Clinical extracorporeal shock wave lithotripsy (ESWL) treatment to ablate kidney stones can cause acute damage to the renal microvasculature. Accumulation of continued treatment with shockwave therapy can lead to chronic damage to the kidney, and lead to clinical hypertension. Shockwaves have been shown to stimulate endothelial cells to release superoxide (SO), which is converted to hydrogen peroxide (H2O2), and reacts with nitric oxide (NO) to produce peroxynitrite anion (OONO-), creating a powerful oxidant that increases oxidative stress while simultaneously reducing NO bioavailability. Increased oxidative stress during events such as ESWL, also uncouples NO production reaction in endothelial nitric oxide synthase (eNOS), causing eNOS to produce SO instead of NO, exacerbating the oxidative insult. NO is an essential signaling molecule responsible for vasodilation, which also functions in inhibiting platelet adhesion and reducing leukocyte-endothelial interactions. This increased oxidative stress, decreased NO bioavailability, and the direct physical force of the shock wave causes prolonged renal vasodilation and eventually vascular endothelial dysfunction in the renal vasculature. Protein kinase C epsilon (PKC-ε) positively regulates eNOS, increasing its activity regardless of whether eNOS is producing SO or NO. We hypothesized that the PKC-ε peptide inhibitor (N-Myr-EAVSLKPT, MW = 1054) would attenuate ESWL-induced increased H2O2 release and increase NO release compared to ESWL-saline control rats, while the PKC-ε peptide activator (N-Myr-HDAPIGYD, MW 1097) would increase ESWL-induced H2O2 release and reduce NO release. H2O2 and NO was measured in real-time by inserting a H2O2 or NO microsensor (100 um diameter) into the left renal vein in anesthetized male Sprague-Dawley rats. ESWL treatment was administered with 16 kV shock waves for 13 minutes in a period of 500 shocks at 60 beats/min then 500 shocks at 120 beats/min by an Epos Ultra lithotripter. Immediately post-ESWL treatment, saline or drug was infused through the external jugular vein. Infusion of PKC-ε inhibitor in ESWL-treated rats significantly reduced H2O2 release (n = 5) from 5 minutes (p < 0.05) to 30 minutes (p < 0.01) compared to ESWL-saline controls (n = 5). PKC-ε inhibitor also significantly increased NO release (n = 5) from 5 minutes (p < 0.01) to 30 minutes (p < 0.01) compared to ESWL-saline controls (n = 5). Contrary to the hypothesis that PKC-ε activator would increase H2O2 release and reduce NO release, results from PKC-ε activator showed a similar but not statistically significant different trend to ESWL-saline controls in H2O2 release (n = 5) and NO release (n = 5). The data shows that inhibition of PKC-ε effectively decreases ESWL-induced increased H2O2 release and significantly restores NO release, which suggests that uncoupled eNOS is a significant source of oxidative stress during ESWL treatment. This results in decreased oxidative stress, attenuating endothelial dysfunction and further damage to the renal microvasculature.