Understanding the Exercise-Hypertension Paradox: Implication for Rehabilitation

了解运动-高血压悖论：对康复的影响

• 批准号: 8677130
• 负责人: Joel Douglas Trinity
• 金额: --
• 依托单位: VA SALT LAKE CITY HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8677130
• 关键词: Acute; Affect; Aging; American; Antioxidants; Ascorbic Acid; Attenuated; Blood Pressure; Blood flow; Cardiovascular Diseases; Cardiovascular system; Clinical; Combined Modality Therapy; Complex; Coronary heart disease; Data; Development; Diagnosis; Doppler Ultrasound; Effectiveness; Endothelial Cells; Endothelium; Etiology; Exercise; Exercise Tolerance; Exhibits; Feedback; Fiber; Free Radicals; Goals; Health; Healthcare Systems; Heart failure; Human; Hypertension; Impairment; Individual; Kidney; Laboratories; Left; Leg; Mechanoreceptors; Medical; Methods; Movement; Muscle; Myocardial Infarction; Oral; Oxidative Stress; Patients; Performance; Peripheral arterial disease; Physical activity; Physiological; Play; Population; Prevention; Production; Reflex action; Rehabilitation therapy; Risk; Risk Factors; Role; Skeletal Muscle; Source; Stroke; Testing; Thioctic Acid; Training; Vascular Endothelial Cell; Vascular Endothelium; Veins; Venous; Veterans; Work; antioxidant therapy; base; cardiovascular risk factor; design; hemodynamics; hypertension treatment; improved; insight; interest; novel; novel strategies; novel therapeutic intervention; practical application; programs; public health relevance; response; treatment strategy

DESCRIPTION: Nearly 37% of all Veterans are clinically hypertensive, making hypertension the most common medical condition in the VA Health Care System. Importantly, of the 67 million Americans diagnosed with hypertension less than half are being effectively treated for their condition4. Hypertension constitutes a major risk factor for cardiovascular disease and when left untreated leads to the development of heart failure, coronary heart disease, peripheral artery disease, stroke, and renal disease5, 6. Exercise and regular physical activity are considered the cornerstones of prevention and management of hypertension 5-7. However, individuals with hypertension exhibit exercise intolerance characterized by impaired skeletal muscle blood flow and heightened afferent fiber sensitivity leading to an exaggerated or greater than normal physiologic increase in blood pressure during exercise (i.e. exercise pressor reflex or EPR)8-10. This imbalance between the beneficial effects of exercise and exercise intolerance creates an interesting paradox, the causes and consequences of which are poorly understood. The etiology of hypertension is undoubtedly complex, however a common denominator in this condition, elevated oxidative stress, may contribute to impaired muscle blood flow and heightened skeletal muscle afferent feedback leading to the exaggerated EPR11-13. Previous work from our laboratory and others suggests that elevated oxidative stress associated with aging impairs muscle blood flow 14, 15. Additionally, free radicals, the initiators of oxidative stress, can diretly stimulate skeletal muscle afferent fibers leading to the exaggerated EPR11. Importantly, the role of oxidative stress in regulating muscle blood flow and afferent fiber function in human hypertension has not been determined. Preliminary studies support a significant role of oxidative stress in impairing muscle blood flow and contributing to the exaggerated EPR in hypertension. With this information as context two aims are proposed that will systematically identify the consequences of elevated oxidative stress in hypertension. Specific Aim 1 will determine the consequences of oxidative stress by examining how elevated free radicals contribute to heightened skeletal muscle afferent feedback and impaired muscle blood flow during exercise in hypertension leading to the exaggerated EPR. Additionally, vascular endothelial cells collected from an antecubital vein will provide novel insight regarding the endothelium as potential source of elevated oxidative stress in hypertension. Specific Aim 2 will determine the effectiveness of combined antioxidant therapy and exercise rehabilitation in the treatment of hypertension. The overall goal of this proposal is to provide novel information regarding the role of oxidative stres as a critical regulator of cardiovascular and hemodynamic responses to exercise in hypertension. By identifying potential causes and consequences of oxidative stress, important insight will be gained facilitating the development of novel approaches and therapeutic strategies for the treatment of hypertension. Importantly, the practical applications tested in these studies (i.e. antioxidant treatment and combined exercise rehabilitation) are designed to identify and document effective countermeasures to aid in the treatment and management of hypertension allowing for the safe performance of exercise in a large number of Veterans.

产品说明： 近37%的退伍军人是临床高血压，使高血压在VA医疗保健系统最常见的医疗条件。重要的是，在6700万被诊断患有高血压的美国人中，只有不到一半的人得到了有效的治疗。高血压是心血管疾病的主要危险因素，如果不及时治疗，会导致心力衰竭、冠心病、外周动脉疾病、中风和肾脏疾病的发生5，6。运动和定期的身体活动被认为是预防和管理高血压的基石5-7。然而，患有高血压的个体表现出运动不耐受，其特征在于受损的骨骼肌血流和升高的传入纤维敏感性，导致运动期间血压的过度或大于正常生理增加（即运动加压反射或EPR）8-10。运动的有益效果和运动不耐受之间的这种不平衡造成了一个有趣的悖论，其原因和后果知之甚少。高血压的病因无疑是复杂的，然而，这种情况的共同点是氧化应激升高，可能导致肌肉血流量受损和骨骼肌传入反馈增强，导致EPR升高11 -13。我们实验室和其他人以前的工作表明，与衰老相关的氧化应激升高会损害肌肉血流量14，15。此外，自由基，氧化应激的引发剂，可以直接刺激骨骼肌传入纤维，导致夸大的EPR 11。重要的是，氧化应激在调节肌肉血流量和传入纤维功能在人类高血压中的作用尚未确定。初步研究支持氧化应激在损害肌肉血流量和促进高血压的EPR放大中的重要作用。有了这些信息作为背景，提出了两个目标，将系统地确定高血压中氧化应激升高的后果。具体目标1将确定氧化应激的后果，通过检查如何升高的自由基有助于提高骨骼肌传入反馈和受损的肌肉血流量在高血压运动过程中，导致夸大的EPR。此外，从肘前静脉收集的血管内皮细胞将提供关于内皮作为高血压中氧化应激升高的潜在来源的新见解。具体目标2将确定联合抗氧化治疗和运动康复治疗高血压的有效性。这项建议的总体目标是提供新的信息氧化应激的作用，作为一个关键的调节心血管和血液动力学反应的运动高血压。通过确定氧化应激的潜在原因和后果，将获得重要的见解，促进高血压治疗的新方法和治疗策略的发展。重要的是，这些研究中测试的实际应用（即抗氧化剂治疗和联合运动康复）旨在确定和记录有效的对策，以帮助治疗和管理高血压，从而使大量退伍军人能够安全地进行运动。