Development of a model for evaluation of the wear and cutting efficiency of nickel-titanium engine-driven files

Abstract

Diabetic patients often develop hypertension as a result of enhanced renal sodium reabsorption and altered sodium balance. Because nitric oxide (NO) is a critical mediator of sodium han.dling, our goal was to elucidate the diabetes-induced alterations in the NO system. The medullary thick ascending limb (mT AL) of Henle's loop expresses all three isoforms of NO synthase (NOS1, NOS2, and NOS3). Under physiological conditions, NO inhibits sodium reabsorption in the mTAL, while superoxide (02•) promotes it. The balance between NO and 0 2- is critical for controlling sodium reabsorption in the TAL, which is responsible for reabsorbing twenty to thirty percent of filtered sodium. Therefore, the objectives of this study were to examine the regulation ofNOS enzyme expression, NOS enzyme activity, NO production, and NO bioavailability as well·as the influence of NO on sodium reabsorption in the mT AL under diabetic conditions. Diabetes is a state of increased 0 2- production. 0 2- scavenging reduces NO bioavailability. We hypothesized that NO production would be enhanced in the mTAL during diabetes. We found that although NO production was enhanced in the mTAL during diabetes, NO bioavailablity was blunted due to increased 0 2- production. NOS 1 and NOS3 activities are regulated by changes in phosphorylation status. Immunohistochemical analysis suggests that protein phosphatase 2 B (PP2B; calcineurin) is upregulated in the mTAL in diabetes. We hypothesized that NOS activity and NO production was upregulated in a PP2B-dependent manner in the mTAL during diabetes. We found that NOS 1 and NOS2-dependent NO production were increased in a PP2Bdependent manner. Additionally, we examined the role ofNO in the regulation of sodium reabsorption in the mTAL during diabetes. We hypothesized that NO production would blunt sodium reabsorption. NOS 1 and NOS2-derived NO production blunted sodium reabsorption in the mT AL under diabetic conditions, but only in the presence of a 02- inhibitor to prevent scavenging of NO. In conclusion, we have revealed important mechanisms that are critical to the regulation ofNO production in the mTAL during diabetes.. These studies also enhanced our understanding of the regulation of sodium transport by NO in the mTAL, specifically under diabetic conditions.