Tetrahydrobiopterin (BH4) attenuates extracorporeal shock wave lithrotripsy (ESWL) induced blood nitric oxide (NO) level reduction in the renal vein

Abstract

ESWL, a therapy for kidney stone ablation clinically, may lead to hypertension. This may be due to kidney vascular endothelial dysfunction, which is characterized as increased oxidative stress and decreased endothelial NO synthase (eNOS)‐derived NO bioavailability. We hypothesized that ESWL would decrease NO in rat renal veins. By contrast, rats given BH4, the essential cofactor of eNOS, would attenuate ESWL‐induced decrease in NO. Blood NO was directly measured in real‐real time by inserting a NO microsensor (100μm diameter) into the left renal vein in the anesthetized rat. ESWL treatment consisted of 1,000 shocks with a 16kV shock wave for approximately 13 minutes. Saline or BH4 was injected via the jugular vein immediately post‐ ESWL and at the same time point for the non‐ESWL control rats. Our preliminary data showed that saline ESWL‐treated rats (n=3) reduced blood NO by 107–203 nM, which is significantly reduced compared to non‐ESWL controls (n=6, p< 0.05) during the 30 min post‐ESWL. By contrast, blood NO level in rats given BH4 under ESWL conditions (6.5 mg/kg, n=4, p<0.05) only decreased by 15–19 nM post‐ESWL compared to saline ESWL. This data supports that ESWL treatment decreases NO bioavailability, which may be due to decreased BH4 content. Future studies are aimed at evaluating blood oxidative stress levels (i.e. hydrogen peroxide) when given ESWL or ESWL+BH4.