权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

SYSTOLIC CARDIAC FUNCTION IN OBESITY AND EXERCISE

肥胖和运动中的心脏收缩功能

基本信息

批准号：
6783323
负责人：
JOAN F CARROLL
金额：
$ 8.83万
依托单位：
UNIVERSITY OF NORTH TEXAS HLTH SCI CTR
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-09-01 至 2006-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6783323
关键词：
beta adrenergic agent beta adrenergic receptor cardiovascular disorder cardiovascular function exercise heart catheterization heart contraction hemodynamics hypertension laboratory rabbit medical complication neuroendocrine system obesity tachycardia telemetry western blottings

项目摘要

DESCRIPTION (Adapted from applicant's abstract) The candidate's immediate career goals are to study the role of the beta-receptor signaling pathway in mediating systolic dysfunction in obesity, and the role of exercise training in attenuating obesity-related cardiovascular defects. The Department of Integrative Physiology at the University of North Texas Health Science Center is uniquely suited to help the candidate achieve these goals. Within the department, there is a wide variety of expertise in human, animal, in vivo, and in vitro studies in cardiovascular physiology and endocrinology. This will aid in developing expertise with a variety of surgical, laboratory, and assay techniques to study cardiac function. Further, the Cardiovascular Research Institute at the University of North Texas Health Science Center provides access to research efforts of molecular biologists, pharmacologists, physiologists and physicians from within the institution and from nearby institutions. This will benefit career development by providing opportunities to integrate knowledge from many fields which impact cardiovascular research. The current proposal has three major goals: 1) to determine mechanisms associated with reduced cardiac contractile responsiveness to beta-adrenergic stimulation in obesity, 2) to determine the role of exercise training in attenuation of obesity-induced abnormalities in cardiac function, and 3) to determine the role of obesity, separate from hypertension, in contributing to systolic dysfunction in sedentary and trained animals. The investigators hypothesize that there are multiples sites of decreased activity in the beta- signaling pathway in obesity. Thus, they will use the rabbit method of dietary-induced obesity to compare function of lean animals with that of obese animals after 12 weeks of a high fat diet. They will use the Langendorff isolated heart preparation and appropriate assay and western blotting techniques to analyze the role of the beta-receptor and four sites of post- receptor activity in contributing to cardiac abnormalities in obesity. The investigators also hypothesize that exercise training during the development of obesity will attenuate or prevent obesity-related cardiovascular abnormalities. They will determine whether exercise training will 1) reduce obesity-related hypertension, resting tachycardia, and neurohumoral activation, and 2)attenuate obesity-related decreases in responsiveness to beta-adrenergic stimulation. They will examine hemodynamics and neurohumoral activation in vivo and use the isolated heart preparation to determine the role of exercise training in increasing responsiveness to beta-adrenergic stimulation. Finally, they hypothesize that obesity has an independent effect on cardiac hypertrophy and systolic dysfunction. They will test this hypothesis by maintaining blood pressure at control levels as obesity develops before testing for responsiveness to beta-adrenergic stimulation. Insight into mechanisms whereby obesity increases risk for congestive heart failure may lead to advances in therapeutic modalities for prevention and treatment of heart failure in obese patients. Information on mechanisms whereby exercise training may improve cardiovascular risk profile and cardiac performance in obesity may help reduce risk for development of cardiovascular diseases in obesity. Because such a large segment of the American population is overweight or obese, the knowledge and insight gained from these studies can have far-reaching effects.

描述（改编自申请人的摘要）候选人的近期职业目标是研究β受体信号通路在介导收缩期中的作用肥胖症的功能障碍以及运动训练在减轻肥胖症中的作用肥胖相关的心血管缺陷。综合系北德克萨斯大学健康科学中心的生理学是独一无二的适合帮助候选人实现这些目标。在部门内部，在人类、动物、体内和体外方面有各种各样的专业知识心血管生理学和内分泌学研究。这将有助于发展各种手术、实验室和化验方面的专业知识研究心脏功能的技术。此外，心血管研究北德克萨斯大学健康科学中心研究所提供获得分子生物学家、药理学家的研究成果，来自机构内部和附近的生理学家和医生机构。这将通过提供机会有利于职业发展整合影响心血管研究的多个领域的知识。目前的提案有三个主要目标：1）确定机制与β-肾上腺素能心脏收缩反应性降低有关肥胖刺激，2) 确定运动训练在肥胖中的作用减轻肥胖引起的心功能异常，3) 确定肥胖（与高血压分开）在促进久坐和训练有素的动物的收缩功能障碍。调查人员假设β-中存在多个活性降低的位点肥胖中的信号通路。因此，他们将使用兔子方法饮食引起的肥胖，比较瘦动物和肥胖动物的功能高脂肪饮食 12 周后的动物。他们将使用 Langendorff 离体心脏制备和适当的测定和蛋白质印迹技术分析 β 受体和四个后位点的作用受体活性导致肥胖症的心脏异常。这研究人员还假设，在发育过程中进行运动训练肥胖会减轻或预防肥胖相关的心血管疾病异常。他们将确定运动训练是否会 1) 减少肥胖相关高血压、静息心动过速和神经体液激活，以及2）减轻肥胖相关的反应性下降 β-肾上腺素能刺激。他们将检查血流动力学和神经体液体内激活并使用离体心脏制剂来确定运动训练在提高β-肾上腺素能反应性中的作用刺激。最后，他们假设肥胖具有独立的影响心脏肥大和收缩功能障碍。他们将测试这个随着肥胖的发展，将血压维持在控制水平的假设在测试对β-肾上腺素能刺激的反应之前。洞察力肥胖增加充血性心力衰竭风险的机制可能会导致预防和治疗疾病的治疗方式取得进展肥胖患者的心力衰竭。有关锻炼机制的信息训练可以改善心血管风险状况和心脏功能肥胖可能有助于降低患心血管疾病的风险肥胖。因为美国人口中有很大一部分是超重或肥胖，从这些研究中获得的知识和见解可以具有深远的影响。