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ADRENERGIC CONTROL OF BLOOD VESSELS DURING AGING

衰老过程中肾上腺素对血管的控制

基本信息

批准号：
3116865
负责人：
SUE P DUCKLES
金额：
$ 6.63万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
依托单位国家：
美国
项目类别：
财政年份：
1985
资助国家：
美国
起止时间：
1985-07-01 至 1987-04-30
项目状态：
已结题

项目摘要

Little reliable data currently exists to support the prevailing concept that adrenergic control of vascular smooth muscle becomes less effective with age. Therefore, various components of the adrenergic neuroeffector mechanism of vascular smooth muscle will be studied in vivo and in vitro. Young, mature and senescent rats will be studied in order to answer three questions: 1. Does adrenergic nerve function alter with advancing age? Norepinephrine (NE) content and neuronal accumulation of metaraminol will be measured as indices of adrenergic nerve density. The fraction of total endogenous NE content released during nerve stimulation will be determined in vitro, and the effectiveness of pre-synaptic feedback mechanisms evaluated. 2. Does vascular smooth muscle reactivity change with advancing age? Classical pharmacological techniques involving measurement of vascular smooth muscle contraction and relaxation will be used to assess changes in both alpha and beta adrenergic receptors. Smooth muscle responsiveness to adrenergic nerve stimulation will be assessed in vitro, and the role of the endothelium in smooth muscle relaxation evaluated. 3. Can these functional changes be demonstrated in vivo? Turnover of NE will be evaluated in vivo using a steady state technique. Elucidation of possible age-related alterations in adrenergic control of vascular smooth muscle is vital to understanding how cardiovascular homeostasis is maintained in elderly individuals as well as to designing appropriate therapy for a host of cardiovascular diseases.

目前几乎没有可靠的数据来支持流行的概念肾上腺素能对血管平滑肌的控制变得不那么有效随年龄因此，肾上腺素能神经效应器的各种成分血管平滑肌的机制将在体内和体外进行研究。将研究年轻、成熟和衰老的大鼠，以回答三个问题问题：1. 肾上腺素能神经功能随年龄增长而改变吗？去甲肾上腺素（NE）含量和间羟胺的神经元蓄积将可以作为肾上腺素能神经密度的指标来测量。占总数的比例将测定在神经刺激期间释放的内源性NE含量以及突触前反馈机制的有效性评估。 2. 血管平滑肌反应性是否随年龄增长？涉及测量的经典药理学技术血管平滑肌收缩和舒张的变化将用于评估 α和β肾上腺素能受体的变化。平滑肌对肾上腺素能神经刺激的反应性将在体外评估，并评价内皮在平滑肌舒张中的作用。 3. 这些功能性变化能否在体内得到证实？营业额将使用稳态技术在体内进行评价。阐明肾上腺素能对血管平滑肌的控制可能与年龄有关肌肉对于了解心血管动态平衡至关重要维持在老年人以及设计适当的治疗多种心血管疾病。