Microcirculation in Health and Disease

健康与疾病中的微循环

• 批准号: 7583381
• 负责人: ROBERT L HESTER
• 金额: $ 37万
• 依托单位: UNIVERSITY OF MISSISSIPPI MED CTR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7583381
• 关键词: Acute; Animal Model; Animals; Arachidonic Acids; Attenuated; Biochemical; Blood Glucose; Blood Vessels; Blood flow; Body Weight; Cardiovascular Diseases; Cardiovascular system; Chronic; Clinical Trials; Data; Disease; Epoprostenol; Exercise; Glucose; Goals; Health; Human; Hyperemia; Hyperglycemia; Hyperlipidemia; Hypertension; In Vitro; Insulin; Insulin Resistance; Laboratories; Link; Lipids; Mediating; Metabolic; Metabolism; Microcirculation; Modeling; Muscle; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Oxidative Stress; Partner in relationship; Patients; Persons; Physiological; Potassium Channel; Prostaglandin H2; Prostaglandins I; Publishing; Reactive Oxygen Species; Receptor Activation; Reporting; Risk Factors; Skeletal Muscle; Techniques; Testing; Thromboxane Receptor; Thromboxanes; Tissues; Training; United States; United States National Institutes of Health; Vasoconstrictor Agents; Vasodilation; Weight maintenance regimen; Work; Zucker Rats; arteriole; base; blood glucose regulation; improved; in vivo; insight; muscle metabolism; prevent; programs; public health relevance; receptor; research study; response; tempol; vasoconstriction

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. In response to exercise, skeletal muscle blood flow increases dramatically through a functional vasodilation of the arterioles. We have demonstrated that arachidonic acid metabolites are important in the control of muscle blood flow. The studies in the current proposal will extend these studies and determine the mechanisms by which chronic exercise improves functional vasodilatory in obesity. Obesity is increasing at an alarming rate in the United States and is a major risk factor for a variety of cardiovascular diseases. NIH has initiated clinical trials to determine if exercise training improves cardiovascular health in persons who have both Type 2 diabetes and hypertension, conditions that are prevalent in obesity. Obese humans have an impaired ability to increase muscle blood flow in response to exercise, and the mechanisms underlying this abnormal increase in blood flow (functional hyperemia) are unclear. An impaired functional hyperemia could potentially prevent the obese patient from adequate exercise, a therapy known to improve glucose, lipid and weight control. Therefore, a better understanding of the mechanisms underlying improved functional hyperemia by chronic exercise training in obesity is important. Our recent work has demonstrated that, in obesity, there is an altered arachidonic acid metabolism, resulting in an impaired blood flow response to acute exercise. We have also demonstrated that chronic exercise training improves functional vasodilatory responses in an animal model of obesity. Based on our published and preliminary data the overall goal of this proposal is to test the central hypothesis that chronic exercise training will improve functional vasodilation through improvements in PGI2 vasodilatory responses and decreases in thromboxane vasoconstrictor responses. We propose that these alterations in arachidonic acid metabolism are due to hyperglycemic/hyperlipidemic induced increases in reactive oxygen species. The proposed studies will utilize in vivo and in vitro microcirculatory techniques to provide new and important insights into mechanisms by which chronic exercise training improves functional vasodilatory responses in obesity. PUBLIC HEALTH RELEVANCE: Obesity is increasing at an alarming rate in the United States and is a major risk factor for a variety of cardiovascular diseases. Obese humans have an impaired ability to increase muscle blood flow in response to exercise, which could prevent the obese patient from adequate exercise, a therapy known to improve the elevated glucose, lipids and body weight associated with obesity. Therefore, a better understanding of the mechanisms by which chronic exercise training improves muscle blood flow in obesity is important.

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液流动与组织代谢状态联系起来的生理机制。作为对运动的反应，骨骼肌的血流量通过小动脉的功能性血管扩张而显著增加。我们已经证明花生四烯酸代谢产物在肌肉血流控制中是重要的。目前提案中的研究将扩展这些研究，并确定慢性运动改善肥胖症患者功能性血管扩张的机制。肥胖在美国正以惊人的速度增长，是各种心血管疾病的主要风险因素。美国国立卫生研究院启动了临床试验，以确定运动训练是否改善了患有2型糖尿病和高血压的人的心血管健康，这两种疾病在肥胖症中很常见。肥胖的人运动后增加肌肉血流量的能力受损，这种血流量异常增加(功能性充血)的机制尚不清楚。功能性充血受损可能会阻止肥胖患者进行足够的运动，这是一种已知的改善血糖、血脂和体重控制的疗法。因此，更好地了解慢性运动训练改善肥胖症功能性充血的机制是重要的。我们最近的工作表明，在肥胖症患者中，花生四烯酸代谢发生了变化，导致对急性运动的血流反应受损。我们还证明，在肥胖动物模型中，慢性运动训练可以改善功能性血管扩张反应。基于我们已发表的和初步的数据，这项建议的总体目标是检验这一中心假设，即长期运动训练将通过改善PGI2血管扩张反应和减少血栓素血管收缩反应来改善功能性血管扩张。我们认为花生四烯酸代谢的这些变化是由于高血糖/高脂诱导的活性氧增加所致。这项拟议的研究将利用体内和体外微循环技术，为慢性运动训练改善肥胖症患者功能性血管扩张反应的机制提供新的重要见解。与公共健康相关：肥胖在美国正以惊人的速度增长，是各种心血管疾病的主要风险因素。肥胖人类因运动而增加肌肉血流量的能力受损，这可能会阻止肥胖患者进行足够的运动，这是一种已知的改善与肥胖相关的血糖、血脂和体重升高的疗法。因此，更好地了解慢性运动训练改善肥胖症患者肌肉血流的机制是很重要的。