AIRPUFF STRESS PHENOTYPE AND GENETIC HYPERTENSION

气喘应激表型和遗传性高血压

• 批准号: 6327710
• 负责人: Morton P Printz
• 金额: $ 25.51万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6327710
• 关键词: baroreceptors; baroreflex; brain metabolism; cardiovascular function; cardiovascular stress test; disease /disorder etiology; environmental stressor; familial hypertension; fos protein; gene expression; genetic mapping; genetic strain; heart rate; laboratory rat; neuropharmacology; receptor expression; spontaneous hypertensive rat; startle reaction; tissue /cell culture

The objectives of this Project are to utilize a new airpuff stress phenotype to elucidate the neural substrates, pharmacology and genetic basis of abnormal cardiovascular responses to mild stressful stimuli in the Spontaneously Hypertensive Rat (SHR) and to define the usefulness of this new phenotype to an understanding of the etiology of genetic hypertension in rodents and man. The phenotype utilizes an airpuff startle stimulus which elicits a classical startle reaction accompanied by a complex cardiovascular response. The genetic hypertensive rat exhibits aberrant and excessive cardiovascular responses to the stimulus. Central to the studies proposed are recent results demonstrating that the airpuff stimulus activates expression of immunoreactive fos in a subset of brain nuclei in the hypothalamus, midbrain and brainstem in a startle-, strain- and habituation-dependent manner, with greater activation in SHR brain nuclei. Studies will define fos expression in prehypertensive rats, evaluate the effects of the baroreceptor reflex on fos expression and compare brain and spinal fos expression. Double-labeling studies of fos and selected brain receptor systems will probe the pharmacology of responding neurons. Receptor blockade will test the function of double- labeled neurons in target nuclei. In addition, genetic studies of the new phenotype will employ the set of Recombinant Inbred Rat strains. The results of these studies should enhance our knowledge of the role of environmental stress on the etiology of hypertension and related cardiovascular disorders.

该项目的目标是利用新的气吹压力 表型阐明神经底物、药理学和遗传 心血管对轻度应激刺激异常反应的基础 自发性高血压大鼠（SHR）并定义其有用性 这种新的表型有助于理解遗传的病因学 啮齿动物和人类的高血压。该表型利用气吹惊吓 刺激会引起经典的惊吓反应，并伴有 复杂的心血管反应。遗传性高血压大鼠表现 心血管对刺激的异常和过度反应。中央 所提出的研究的最新结果表明，气枪 刺激激活大脑子集中免疫反应性 fos 的表达 下丘脑、中脑和脑干的核团处于惊恐、紧张状态 和习惯依赖方式，SHR 大脑有更大的激活 原子核。研究将定义高血压前期大鼠中 fos 的表达， 评估压力感受器反射对 fos 表达的影响和 比较大脑和脊髓的 fos 表达。 fos的双标记研究 和选定的大脑受体系统将探索药理学 反应神经元。受体阻断将测试双功能 目标细胞核中标记的神经元。此外，新的基因研究 表型将采用一组重组近交系大鼠品系。这 这些研究的结果应该增强我们对 环境压力对高血压病因的影响及相关 心血管疾病。