Synchronized research on endothelial dysfunction and microcirculation structure in dorsal skin of rats with type 2 diabetes mellitus

The aim of this study was to explore changes in the microvascular tone as measured by laser Doppler flowmetry (LDF) and the microcirculation structure of the dorsal skin of rats with type 2 diabetes mellitus. The diabetic rat model was induced by a diet of high-sugar and high-lipid fodder combined with the injection of streptozotocin into the abdominal cavity. Depending on the interval between the development of diabetes and the experiments, the diabetic rats were subdivided into three groups. The evaluation of microvascular tone was based on the amplitude responses of the LDF signal fluctuations in the appropriate frequency range in the dorsal skin of the rats during a thermal test (at 42 °C). The nitric oxide (NO) level in plasma was also used as a marker of endothelial dysfunction. Changes in the microcirculation structure in the diabetic rats were estimated by measuring the microvascular density in the choke vessels of the dorsal skin of the rats. The experimental results with respect to red blood cell (RBC)-related parameters showed decreased hematocrit and hemoglobin levels and increased standard deviation of the width of the RBC distribution in three diabetic rats. The increasing fluctuation amplitudes diminished in the endothelial frequency range in response to the thermal test and this was accompanied by abnormal NO levels in plasma of the diabetic groups as compared with healthy rats. A significant reduction in the microvascular density of the choke vessels of the dorsal skin was found only in the diabetic group at the most advanced stage of diabetes in this experiment. Thus, we suggest that endothelial dysfunction occurs in diabetic rats and changes in the microcirculation structure of the dorsal skin occur in a later stage of diabetes development. A. Photograph of measurement method by using a LDF probe and heating device in the dorsal skin of the rat. B. Dorsal skin LDF signals of a healthy rat during the thermal stimuli test. (a) Blood flow signal record for the test. Wavelet filtration of blood flow signal in (b) myogenic range, (c) neurogenic range, and (d) endothelial range.

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