A vasoprotective role for free‐radical scavenger therapies in chronically hyperglycemic mice

Abstract

The presence of a hydrodynamically relevant endothelial‐cell surface glycocalyx, ~ 0.5 µm thick, is well established under normal physiological conditions. This layer is partially degraded by light‐dye treatment and completely degraded following hyaluronidase treatment. Many complications of diabetes are derived from vascular disease, and the glycocalyx is situated as the first line of defense against vascular damage. Therefore, we seek to establish the effects of hyperglycemia on the glycocalyx and the effectiveness of various therapies. We analyzed data obtained in venules of chronically hyperglycemic NOD mice receiving subsistence levels of insulin therapy, half of which were also treated with synthetic catalytic free radical scavengers (SOD). In mice receiving insulin only, we observed that the glycocalyx thickness is degraded to ~ 0.21 µm (n = 10), compared with ~ 0.48 µm (n = 13) in healthy wild type and NOD mice. This degradation is significant (p < 0.05) and is comparable to that seen after free‐radical damage. In mice also treated with SOD, the glycocalyx thickness was ~ 0.39 µm (n = 10); this is not significantly different from the healthy control group. Furthermore, we seek to link glycocalyx degradation to vascular pathology. Preliminary data suggest that chronic enzymatic degradation results in pathological levels of microalbuminuria, an early indicator of kidney dysfunction due to vascular damage.