ALTERED ARTERIOLAR FUNCTION IN EXPERIMENTAL DIABETES

描述：本提案将研究以下假设： 葡萄糖代谢的代谢异常， 糖尿病（即，高级糖基化反应，从头合成 甘油二酯）导致的表达和/或性质的改变， 细胞外基质蛋白， 小动脉中的机械传导。 然而，同样的新陈代谢 干扰增强血管平滑肌对 收缩激动剂。所提出的实验将考虑 糖尿病对代谢传导和 微血管平滑肌中的药物力学耦合。 的 研究人员建议在几个层面上检验这一假设。 研究将利用链脲佐菌素诱导的糖尿病大鼠模型 正常对照组和实验组 胰岛素或氨基胍治疗。 体内测量 将进行小动脉血压检查，以检查 实验性糖尿病局部血压控制。的影响 实验性糖尿病对阻力力学性能的影响 血管也将在分离的体外制剂中进行评价， 小动脉分离的小动脉制剂将用于 糖尿病免疫组化和原位杂交分析 诱导血管壁基质蛋白的改变，以及 确定这种变化在受损的 机械传导

DESCRIPTION: This proposal will examine the hypothesis that the metabolic abnormalities of glucose metabolism that characterize diabetes (ie, advanced glycosylation reactions, de novo synthesis of diglyceride) lead to alterations in expression and/or nature of extracellular matrix proteins which adversely affect mechanotransduction in arterioles. However, the same metabolic disturbances potentiate the response of vascular smooth muscle to contractile agonists. The experiments proposed will consider the effects of diabetes on both mecahnotransduction and pharmacomechanical coupling in microvascular smooth muscle. The investigator proposes to test this hypothesis on several levels. Studies will utilize the streptozotocin-induced diabetic rat model and normal controls as well as experimental groups receiving insulin or aminoguanidine treatment. In vivo measurements of arteriolar blood pressure will be performed to examine the effect of experimental diabetes on local blood pressure control. The effect of experimental diabetes on the mechanical properties of resistance vessels will also be evaluated in isolated in vitro preparations of arterioles. Isolated arteriolar preparations will be used for immunohistochemical and in situ hybridization analysis of diabetes induced alterations in the vessel wall matrix proteins, and to determine the possible role such changes in impaired mechanotransduction.