PHYSICAL TRAINING & ADRENERGIC RECEPTORS IN HYPERTENSION

体力训练

• 批准号: 3422335
• 负责人: MICHAEL A BERK
• 金额: $ 2.24万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-07-01 至 1986-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3422335
• 关键词: adenylate cyclase; blood pressure; exercise; human subject; hypertension; leukocytes; physical fitness; platelets; radiotracer

Essential hypertension, accounting for greater than 90% of all hypertension, affects between 15 and 20% of all adults and is a significant risk factor for excess morbidity and mortality due to arteriosclerotic and cerebrovascular disease. Reduction of even mild hypertension has been shown to decrease long-term morbidity and mortality due to vascular disease. Excess sympathetic nervous system activity has been postulated as an etiologic factor in essential hypertension but direct measurement of circulating plasma norepinephrine and epinephrine levels as an indicator of sympathetic dysfunction has been equivocal. Direct studies of adrenergic receptor-effector mechanisms in essential hypertension have been scant but are suggestive of a generalized receptor-effector abnormality in hypertensive subjects. The present study is designed to study the effects of physical training, a modality known to reduce sympathetic activity, on adrenergic-receptor effector mechanisms and their relationship to blood pressure. Beta-2 and alpha-2 adrenergic receptors will be measured on circulating mononuclear leukocytes and platelets, respectively, in untreated hypertensive subjects (n=10) and matched normal controls (n=10) at baseline, after a one-month period with no therapy and after 12 weeks of bicycle ergometer exercise at 60% maximal oxygen consumption for 30 minutes, three times per week. Receptor studies will include standard saturation curves to measure apparent dissociation constant (Kd) and receptor density (Beta max). Beta-2 receptors will be measured with Iodocycopindolol-125, a Beta antagonist, an Alpha-2 receptors with [H-3]-UK-14304, an Alpha-2 agonist. In addition, competition studies will be done in the presence and absence of Gpp(NH)p to determine the percentage of receptors in high and low affinity binding states. Adenylate cyclase activity in response to isoproterenal stimulation (Beta-2) and epinephrine inhibition (Alpha-2) will also be done. It is expected that 1) hypertensive subjects will exhibit altered adrenergic receptor status when compared to normal controls that will correct after physical training and 2) correction of receptor abnormality will be correlated with a decrease in blood pressure.

原发性高血压，占90%以上 高血压，影响15%至20%的所有成年人，是一个重要的 动脉炎导致的发病率和死亡率过高的风险因素， 脑血管疾病 即使是轻微的高血压也会减少， 显示可降低血管性心脏病的长期发病率和死亡率， 疾病 过度的交感神经系统活动被假定为 原发性高血压的病因因素，但直接测量 循环血浆去甲肾上腺素和肾上腺素水平作为 交感神经功能障碍一直是模棱两可的 肾上腺素能的直接研究 原发性高血压的受体效应机制尚不清楚， 提示了一种广泛的受体效应器异常， 高血压患者。 本研究旨在研究体育锻炼对老年人的影响， 已知减少肾上腺素能受体交感神经活动的方式 效应机制及其与血压的关系。 β-2和α-2肾上腺素能受体将在循环中测量。 单核白细胞和血小板，分别在未经治疗的 高血压受试者（n=10）和匹配的正常对照组（n=10）， 基线、1个月无治疗期后和12周后 自行车测力计运动60%最大耗氧量30 分钟，每周三次。 受体研究将包括标准 饱和曲线以测量表观解离常数（Kd），以及 受体密度（β max）。 β-2受体将采用 Iodocycopindolol-125，一种β拮抗剂，一种α-2受体， [H-3]-UK-14304，α-2激动剂。 此外，竞争研究将 在存在和不存在Gpp（NH）p的情况下进行，以确定 高亲和力和低亲和力结合状态的受体。 腺苷酸环化酶 对异丙肾上腺素刺激（Beta-2）和肾上腺素的反应活性 还将进行抑制（Alpha-2）。 预计1） 高血压患者将表现出改变的肾上腺素能受体状态， 与正常对照组相比， 2)受体异常的纠正将与 血压.