Functional hyperemia during metabolic syndrome

描述（由申请人提供）：我们实验室的长期目标是确定将肌肉血流与组织代谢状态联系起来的生理机制，以及这些机制在病理生理条件下如何改变。例如，肥胖症与高血压、血脂异常和II型糖尿病相关，II型糖尿病是通常被称为代谢综合征的病症的集合，影响大约4500万美国居民。内皮功能障碍是代谢综合征的重要组成部分。血糖稳态受损和活性氧生成升高可能是这些患者内皮功能障碍的重要因素。本发明采用动物模型，肥胖Zucker大鼠，其表现出增加的食物消耗，并迅速发展为肥胖、II型糖尿病和高血压（即，代谢综合征）。因此，Zucker大鼠提供了一个有用的工具，用于研究在西方社会流行率迅速增长的病理生理条件下的血管功能。本研究中的实验将为代谢综合征模型中功能性充血受损的细胞机制以及运动训练改善内皮功能的细胞机制提供重要的新信息。

DESCRIPTION (provided by applicant): The long-term goal of our laboratory is to define the physiological mechanisms linking muscle blood flow to the metabolic state of the tissue, and how these mechanisms are altered under pathophysiological conditions. For example, obesity is associated with hypertension, dyslipidemia, and type II diabetes, a collection of conditions often referred to as metabolic syndrome affecting approximately 45 million US residents. Endothelial dysfunction is major component of metabolic syndrome. Impaired blood glucose homeostasis and elevated reactive oxygen species generation may be important factors in the endothelial dysfunction seen in these individuals. The present proposal employs an animal model, the obese Zucker rat which exhibits increased food consumption, and rapidly develops obesity, type II diabetes, and hypertension (i.e., metabolic syndrome). Thus, the Zucker rat provides a useful tool for the study of vascular function during a cohort of pathophysiological conditions that are rapidly growing in prevalence in western society. The experiments in this proposal will provide important new information concerning the cellular mechanism(s) of impaired functional hyperemia in a model of metabolic syndrome, and the cellular mechanisms by which exercise training improves endothelial function.