ESTROGEN EFFECT ON THE SYMPATHETIC NERVOUS SYSTEM

雌激素对交感神经系统的影响

• 批准号: 2734929
• 负责人: CARMEN HINOJOSA-LABORDE
• 金额: $ 10.6万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-07-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2734929
• 关键词: baroreceptors; cardiovascular function; estrogens; female; gamma aminobutyrate; gender difference; genetic strain; high performance liquid chromatography; hormone regulation /control mechanism; hypertension; hypothalamus; kidney function; laboratory rat; neuroregulation; norepinephrine; preeclampsia; sex hormones; sympathetic nervous system

The applicant's immediate goals are to identify fundamental differences in the neural control of the sympathetic nervous system between male and female rats as it pertains to the development of hypertension. The applicant's long-term goals are to investigate the role of sex hormones on cardiovascular and renal regulation in pregnancy with a special interest in how cardiovascular and renal regulatory mechanisms are altered in the development of preeclampsia. This award will enhance the applicant's development as an independent investigator by allowing the applicant 1) to learn various techniques critical in evaluating the neural control of the sympathetic nervous system and combine these techniques with those in which the applicant is already proficient to attain her research goals; 2) to work in an environment which allows interaction with scientists from several departments knowledgeable in the area of neural mechanisms of hypertension; 3) to obtain preliminary data which is critical for a strong NIH - FIRST Award application. In human essential hypertension males develop higher levels of blood pressure than females. It has been postulated that estrogen protects against the development of hypertension. The first goal of this project is to test the hypothesis that estrogen alters the regulation of the sympathetic nervous system such that female rats more efficiently decrease sympathetic nerve activity in response to acute activation of arterial and cardiopulmonary baroreceptors resulting in an attenuated hypertension in Dahl salt-sensitive (S) females. The second goal is to propose and define a centrally mediated neural mechanism by which the sympathetic nervous system can be inhibited by estrogen. The hypothesis to be tested is that a noradrenergic-gamma-aminobutyric acid (GABA)ergic pathway exists in the anterior hypothalamus which is involved in sympathoinhibition which can be activated by estrogen. Central microinjection studies and microdialysis studies to measure the release of norepinephrine and GABA in the anterior hypothalamic area are proposed to establish the existence of a noradrenergic-GABAergic sympathoinhibitory relationship. Additional experiments using microinjections of noradrenergic agonists and antagonists as well as GABAergic agonists and antagonists will determine if estrogen stimulates the noradrenergic and/or the GABAergic component of the sympathoinhibitory pathway during basal conditions and during baroreflex activation.

申请人的直接目标是确定 男性和男性之间交感神经系统的神经控制 雌性大鼠与高血压的发展有关。这 申请人的长期目标是调查性激素在 怀孕的心血管和肾脏调节，特别感兴趣 在心血管和肾脏调节机制中如何改变 子痫前期的发展。该奖项将增强申请人的 通过允许申请人的发展作为独立研究者的发展1） 学习各种技术在评估神经控制 交感神经系统，并将这些技术与其中的技术相结合 申请人已经熟练地实现了她的研究目标； 2） 在允许与科学家互动的环境中工作 在神经机制领域知识渊博的几个部门 高血压; 3）获得初步数据，这对于强大的数据至关重要 NIH-第一个奖项申请。 在人类基本高血压中，雄性会出现更高水平的血液 压力比女性。有人认为雌激素可以保护 反对高血压的发展。这个项目的第一个目标是 测试雌激素改变调节的假设 交感神经系统使雌性大鼠更有效地减少 响应动脉急性激活和 心肺压力感受器导致高血压减弱 达尔盐敏感的女性。第二个目标是提出和定义 一种交感神经的中央介导的神经机制 雌激素可以抑制系统。要检验的假设是 甲肾上腺素能 - 氨基氨基丁酸（GABA）ERGIC途径存在于 下丘脑涉及交感神经的前丘脑 被雌激素激活。中央显微注射研究和微透析 测量去甲肾上腺素和GABA在前部的释放的研究 建议下丘脑区域建立A的存在 去甲肾上腺素能抑制性抑制性关系。 额外的 使用去甲肾上腺素激动剂的显微注射和 拮抗剂以及GABA能激动剂和拮抗剂将确定 如果雌激素刺激去甲肾上腺素能和/或GABA能成分 在基础条件下和期间 BaroreFlex激活。