Integrative Cardiovascular Control During Exercise in Hypertension

高血压运动期间的综合心血管控制

• 批准号: 7860572
• 负责人: Donal S O'Leary
• 金额: $ 38万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7860572
• 关键词: Acute; Address; Adult; Affect; Anesthesia procedures; Animal Model; Animals; Arts; Atherosclerosis; Baroreflex; Beds; Blood Circulation; Blood Pressure; Blood Vessels; Blood flow; Buffers; Canis familiaris; Cardiac; Cardiac Output; Cardiovascular Diseases; Cardiovascular system; Cerebral Ischemia; Chronic; Complex; Congestive Heart Failure; Conscious; Coronary; Coupled; Coupling; Depressed mood; Disease; Event; Exercise; Heart; Heart Hypertrophy; Heart Rate; Hour; Human; Hypertension; Kidney Diseases; Laboratories; Lead; Left Ventricular Function; Mediating; Minority; Modeling; Moderate Exercise; Monitor; Muscle; Myocardial Infarction; National Heart, Lung, and Blood Institute; Nerve; Operative Surgical Procedures; Patients; Peripheral; Physical activity; Physiological; Population; Probability; Procedures; Reflex action; Regional Blood Flow; Rest; Risk Factors; Role; Skeletal Muscle; Stroke; Techniques; Time; Trauma; Ventricular; Ventricular Function; Workload; afferent nerve; artery occlusion; design; hemodynamics; indexing; innovation; instrument; instrumentation; neuroregulation; pressure; public health relevance; renal artery; research study; response; statistics; vasoconstriction; virtual

DESCRIPTION (provided by applicant): Hypertension affects nearly 1 in 3 of all adults in the U.S. and is well recognized as a major risk factor for a broad range of cardiovascular diseases such as stroke, congestive heart failure, renal disease, and congestive heart failure. Although the beneficial effects of daily exercise are well known, in patients with established hypertension abnormally large increases in sympathetic nerve activity, arterial pressure and heart rate often occur in response to exercise which precludes advisement of any strenuous physical activity due to the dangerous elevations in arterial pressure which increase the probability of sudden, adverse cardiovascular events such as myocardial infarction and stroke. The mechanisms mediating these abnormal cardiovascular responses to exercise in hypertension are virtually unknown. Many studies from a variety of laboratories using a number of species, including humans, have shown that activation of the metabolically sensitive afferents within the active skeletal muscle (termed the muscle metaboreflex) can elicit profound increases in sympathetic nerve activity. Impaired cardiac function in hypertension due to elevated afterload, cardiac hypertrophy, tonic coronary vasoconstriction and impaired ability to increase ventricular contractility may lead to lower skeletal muscle blood flow during dynamic exercise thereby causing excessive activation of the muscle metaboreflex. Furthermore, the mechanisms of the muscle metaboreflex are intimately dependent on the arterial baroreflex. Although, it is known that hypertension impairs baroreflex function at rest, whether exercise further alters baroreflex function in hypertension is unknown. This proposal is focused on determining the role of the muscle metaboreflex in mediating the altered cardiovascular response to dynamic exercise and the involvement of the arterial baroreflex in mediating these responses. Our laboratory is uniquely poised to address this issue. Over the last two decades we have developed a powerful and highly innovative and technically complex conscious, chronically instrumented canine model using "state of the art" instrumentation which permits the continuous beat-by-beat monitoring of wide variety of hemodynamic parameters and multiple indices of ventricular function in order to assess the strength and mechanisms of cardiovascular reflexes at rest and during dynamic exercise in normal animals and after induction of disease states. We have now expanded this model to the patho- physiological state of hypertension. Our approach is to study the same animal before and after the induction of hypertension thereby each animal serves as its own control. The significance of the project is underscored by the near total lack of information on the effects of hypertension on cardiovascular responses to exercise and these results may aid in the prescription of exercise regimes for hypertensive patients as well as increasing our understanding of the impact of hypertension on neural control of the circulation during one of the greatest challenges to cardiovascular control - whole body strenuous dynamic exercise. PUBLIC HEALTH RELEVANCE: Hypertension affects nearly 1 in 3 of all adults in the U.S. and is well recognized as a major risk factor for a broad range of cardiovascular diseases such as stroke, congestive heart failure, atherosclerosis, renal disease, and congestive heart failure. Although regular exercise is well known to have a multitude of beneficial effects, in patients with well established hypertension abnormally large increases in arterial pressure and heart rate in response to exercise often occur which may preclude advisement of any strenuous physical activity due to the dangerous elevations in arterial pressure which increase the probability of sudden, adverse cardiovascular events such as myocardial infarction and stroke. The mechanisms mediating these abnormal cardiovascular responses to exercise in hypertension are virtually unknown. This proposal is focused on increasing our understanding of the role of sensory nerves that respond to changes in metabolite concentration in the active muscles and those that sense changes in blood pressure in mediating the abnormal responses to exercise in hypertension.

描述（由申请人提供）：高血压影响了美国所有成年人中的近三分之一，并且被广泛认为是广泛的心血管疾病（例如中风，充血性心力衰竭，肾脏疾病和充血性心力衰竭）的主要危险因素。尽管每日运动的有益影响是众所周知的，但在既有高血压异常大大增加的交感神经活动的患者中，动脉压和心率通常会响应于运动而发生，这阻碍了由于动脉压的危险升高而导致的任何剧烈的体育活动的建议，从而增加了突然的心血管不良事件（例如，诸如心血管疾病之类的不良心血管事件），例如肌肉症状。介导这些异常心血管反应对高血压运动的机制几乎是未知的。许多使用许多物种（包括人类）的实验室的研究表明，活性骨骼肌内代谢敏感的传入（称为肌肉代谢反射）可以引起交感神经活动的大幅增加。由于后负荷增加，心脏肥大，滋补冠状动脉血管收缩和增加心室收缩力的能力受损而导致的高血压中的心脏功能受损可能会导致动态运动过程中骨骼肌血流降低，从而导致肌肉过度激活肌肉的肌肉。此外，肌肉代谢反射的机制密切取决于动脉压力反射。虽然，众所周知，高血压会损害静止的压力反射功能，但运动是否进一步改变了高血压中的压力反射功能。该提案的重点是确定肌肉代谢反射在介导对动态运动的心血管反应改变以及动脉压力反射在介导这些反应中的作用。我们的实验室有独特的准备解决这个问题。在过去的二十年中，我们开发了一种强大的，高度创新性和技术复杂的意识，长期仪器犬模型的模型，它允许对各种各样的血流动力学参数和多种心室功能的多种索引进行连续进行，以评估动态和动态性锻炼的心血管疾病的强度和机制，并在正常的情况下进行锻炼。现在，我们已经将该模型扩展到了高血压的病理生理状态。我们的方法是在诱导高血压之前和之后研究同一只动物，从而作为其自身的控制。该项目的重要性始于几乎完全缺乏有关高血压对运动对运动的影响的信息，这些结果可能有助于为高血压患者的运动体制开处方，以及我们对高血压对循环神经控制的影响的理解，这是对心血管控制最大的挑战，对循环的影响 - 心血管控制最大的挑战。公共卫生相关性：高血压影响美国所有成年人中有近三分之一，被公认为是多种心血管疾病（例如中风，充血性心力衰竭，动脉粥样硬化，肾脏疾病和充血性心力衰竭）的主要危险因素。尽管众所周知，定期运动具有多种有益作用，但对于良好的高血压异常大大增加动脉压和心率而响应运动后，经常会发生这种情况，这可能排除由于动脉压的危险升高而导致的任何剧烈体育活动的建议，这会增加突然的，不良心血管疾病的可能性，例如肌肉无力和骨膜。介导这些异常心血管反应对高血压运动的机制几乎是未知的。该提案的重点是增加我们对活性肌肉中代谢物浓度变化的感觉神经的作用的理解，以及那些感觉在介导高血压运动异常反应时血压变化的感觉。