ALTERED ARTERIOLAR FUNCTION IN EXPERIMENTAL DIABETES

描述：这项提案将检验以下假设： 糖代谢异常的特点是 糖尿病(即高级糖基化反应，从头合成 甘油三酯)导致表达和/或性质的改变 对细胞外基质产生不利影响的蛋白质 微动脉中的机械转导。然而，同样的新陈代谢 干扰增强血管平滑肌对 收缩激动剂。建议的实验将考虑 糖尿病对神经细胞转导和细胞免疫功能的影响 微血管平滑肌中的药力偶联。这个 研究人员建议在几个层面上检验这一假说。 研究将利用链脲佐菌素诱导的糖尿病大鼠模型 和正常对照组以及实验组分别接受 胰岛素或氨基胍治疗。活体测量 将测量小动脉血压，以检查其对 实验性糖尿病对局部血压的控制作用。的影响 实验性糖尿病对力学性能的影响 血管也将在分离的体外制剂中进行评估 小动脉。分离的小动脉准备将用于 糖尿病的免疫组织化学和原位杂交分析 诱导血管壁基质蛋白的改变，并导致 确定这些变化在受损人群中可能起到的作用 机械转导。

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.