PHYSICAL TRAINING & ADRENERGIC RECEPTORS IN HYPERTENSION

原发性高血压，占全部高血压的90%以上 高血压，影响15%到20%的成年人，是一种显著的 动脉硬化性心脏病和高血压引起的高发病率和高死亡率的危险因素 脑血管疾病。即使是轻度高血压的减少也是如此 可降低因血管疾病引起的长期发病率和死亡率 疾病。交感神经系统活动过度被认为是 高血压病的病因，但直接测定 循环血浆去甲肾上腺素和肾上腺素水平可作为 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 高血压的受体-效应机制一直很少，但 提示了一种广泛性受体-效应器异常 高血压受试者。 本研究旨在研究体育锻炼的效果。 肾上腺素能受体上已知的降低交感神经活性的方式 效应机制及其与血压的关系。 将在循环中测量β-2和α-2肾上腺素能受体 未经治疗的单核白细胞和血小板 高血压患者(n=10)和匹配的正常对照组(n=10) 基线，在没有治疗的一个月后和在12周后 自行车最大耗氧量为60%的30次 几分钟，每周三次。受体研究将包括标准 测量表观解离常数(Kd)的饱和曲线和 受体密度(Beta Max)。β-2受体将用来测量 IodocyCopindolol-125，Beta拮抗剂，Alpha-2受体 [H-3]-UK-14304，一种α-2激动剂。此外，竞争研究将 在GPP(NH)p存在和不存在的情况下进行，以确定百分比 处于高亲和力和低亲和力结合状态的受体。腺苷环化酶 刺激异丙肾上腺素(β-2)和肾上腺素后的活动 还将进行抑制(Alpha-2)。预计1) 高血压患者在以下情况下将表现出肾上腺素能受体状态改变 与正常对照组相比，在体育训练后和 2)受体异常的纠正将与减少 血压。

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.