CENTRAL NOREPINEPHRINE RELEASE AND ENVIRONMENTAL STRESS

中枢去甲肾上腺素释放和环境压力

• 批准号: 3366965
• 负责人: NATALIE ALEXANDER
• 金额: $ 15.02万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-07-01 至 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3366965
• 关键词: cardiovascular function; environmental stressor; genetic strain; hypertension; hypothalamus; laboratory rat; neurochemistry; norepinephrine; spontaneous hypertensive rat

This application is based on microdialysis experiments in which NE release was monitored simultaneously from paraventricular (PVN) and posterior nucleus (PH) of the hypothalamus in the freely moving rats before, during and after imposition of a quantifiable, painless, environmental stressor, "shaker stress". Shaker stress cause an immediate pressor effect, heart rate change and increases the release of NE at both hypothalamic sites; after stress mean arterial pressure (MAP) and heart rate (HR) return to control levels but enhanced NE release persists, longer in PH than PVN. Specific aims are focused to test the hypotheses that cardiovascular changes are, in part or totally, independent of hypothalamic NE release during shaker stress and that the pressor response attenuates the hypothalamic NE release. Spontaneously hypertensive rats (SHR) have an exaggerated pressor response to shaker stress. We hypothesize that SHR have a greater and/or different pattern of hypothalamic NE release than controls and that adrenoceptor modulation of release is different in SHR than controls. Finally the mechanism of post-stress, enhanced NE release in PVN and PH will be determined. Protocols require continuous measurement of MAP and HR and the simultaneous collection of 5 minute dialysate samples, obtained with 1 mm long microdialysis probes in PVN and PH, from freely moving rats. Extracellular NE will be measured by sensitive radioenzymatic assay. These studies will provide new data on central integrative mechanisms of noradrenergic and cardiovascular activity in hypertension and during stress.

这一应用基于微透析实验，在微透析实验中，NE释放 从室旁(PVN)和后方同时监测 自由活动大鼠下丘脑核团(PH)的变化 在施加了可量化的、无痛的环境应激源之后， “摇摆器压力”。震动应激引起即刻的升压效应，心脏 改变下丘脑和下丘脑两个部位的NE释放； 应激后，平均动脉压(MAP)和心率(HR)恢复到 控制水平，但增强的NE释放持续存在，在PH组比PVN组持续时间长。 具体的目标是测试心血管疾病的假设 变化部分或完全不依赖于下丘脑NE的释放 在振动筛压力过程中，加压反应会减弱 下丘脑NE释放。自发性高血压大鼠(SHR)有一种 对摇床压力的夸大升压反应。我们假设自发性高血压 下丘脑NE释放模式大于和/或不同于 控制和肾上腺素受体对释放的调节在SHR中是不同的 而不是控制。最后探讨了后应激促进NE释放的机制 在PVN和PH将被确定。协议需要持续测量 MAP和HR的同步采集和5分钟透析液的同时采集 用1毫米长的微透析探头在PVN和PH中获得样品，来自 自由活动的老鼠。细胞外去甲肾上腺素将由敏感仪测定 放射酶分析。这些研究将提供有关中央银行的新数据 去甲肾上腺素能与心血管活动的整合机制 高血压和在压力下。