ETHNIC DIFFERENCES IN AUTONOMIC CARDIOVASCULAR CONTROL

自主心血管控制的种族差异

• 批准号: 2415688
• 负责人: ALASTAIR J. J. WOOD
• 金额: $ 27.76万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-06-01 至 2001-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2415688
• 关键词: African American; adrenergic receptor; alpha adrenergic agent; beta antiadrenergic agent; blood pressure; cardiovascular pharmacology; caucasian American; circadian rhythms; clinical research; electrocardiography; gender difference; hemodynamics; human subject; isoproterenol; norepinephrine; personality; pharmacokinetics; plethysmography; psychological stressor; racial /ethnic difference; sympathetic nervous system; vascular smooth muscle nervous control; vasoconstriction; vasodilation

Cardiovascular disease is a major cause of morbidity and mortality in African-Americans, yet remarkably few mechanistic studies have focussed on this group. We hypothesize that there is enhanced, autonomically-mediated vascular tone in African-Americans; this enhanced tone may play an important role in the pathogenesis of cardiovascular disease. Evidence for interethnic differences includes the demonstration of enhanced pressor responses to psychological stressors, increased sympathetic activity after cold pressor testing, an increased frequency of salt sensitivity, and more recently, our observations 1) that forearm vascular responses to the beta- adrenergic agonist, isoproterenol are attenuated in normotensive African- Americans and 2) that ethnicity and gender both influence the psychological traits associated with adverse cardiovascular outcomes. This project will define the mechanisms for the interethnic differences in the regulation of vascular tone through two specific aims. Our strategy will be (Specific Aim l) to utilize pharmacologic probes, with different receptor and non-receptor modes of action, to localize the sites responsible for the interethnic difference in vasodilation. Thus, the known interethnic differences in cardiovascular responses to stress may reflect differences in autonomic control at multiple levels and based on our preliminary data, we propose that differences in psychological traits may predict autonomically-mediated cardiovascular responses. We will determine (Specific Aim 2) the mechanism(s) of interethnic differences in autonomic reactivity by specifically probing central and peripheral levels of autonomic control, using directly measured muscle sympathetic nerve activity (MSNA) and norepinephrine kinetics to examine interethnic differences in basal awake and asleep sympathetiC activity, in stimulated (physiologic, pharmacologic, psychologic, nociceptive) and inhibited (pharmacologic and baroreflex) sympathetic activity, and in presynaptic receptor sensitivity. By defining the factors contributing to the altered cardiovascular response in African-Americans, physicians will be better able to tailor therapy to this group and reduce their present excessive burden of cardiovascular disease.

心血管疾病是发病率和死亡率的主要原因 非洲裔美国人，但很少有机械研究的重点 这个小组。我们假设有增强的，自主介导的 非裔美国人的血管张力；这种增强的语气可能会发挥 在心血管疾病的发病机理中的重要作用。证据 种族间的差异包括增强式压力的演示 对心理压力源的反应，在 冷压测试，盐灵敏度的频率增加，更多 最近，我们的观察结果1）对β-的前臂血管反应 肾上腺素激动剂，异丙烯醇在非洲正常的非洲 - 美国人和2）种族和性别都影响 与不良心血管结局相关的心理特征。这 项目将定义种族间差异的机制 通过两个特定目的调节血管张力。我们的策略将 是（特定的目标l）使用药物探针，不同 受体和非受体作用模式，以本地位置 负责血管舒张的种族差异。因此， 心血管压力反应的已知种族间差异可能 反映在多个级别的自主控制的差异，并基于 我们的初步数据，我们建议心理特征的差异 可以预测自主介导的心血管反应。我们将 确定（特定目的2）种族间差异的机制 自主反应性通过专门探测中心水平 自主控制，使用直接测量的肌肉交感神经 活性（MSNA）和去甲肾上腺素动力学检查种族间 刺激的基础清醒和入睡的交感神经活动的差异 （生理，药理学，心理学，伤害感受），并抑制 （药理学和巴罗雷诺弗莱克体）交感神经活动，并在突触前 受体灵敏度。通过定义导致更改的因素 非裔美国人的心血管反应，医生会更好 能够为该组定制治疗，并减少目前的过度 心血管疾病的负担。