GENETIC HYPERTENSION AND SYMPATHETIC MECHANISMS

遗传性高血压和交感神经机制

• 批准号: 3353808
• 负责人: NATALIE ALEXANDER
• 金额: $ 14.24万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-01 至 1991-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3353808
• 关键词: blood pressure; catecholamines; familial hypertension; gene expression; genetic strain; laboratory rabbit; molecular pathology; neurogenic hypertension; norepinephrine; nucleic acid probes; sympathetic nervous system

The aims of this proposal are: 1) to identify and start development of genetically hypertensive strains of rabbits with a common congenic control; 2) to determine the number of genes controlling hypertension in each strain; 3) to make physiological and biochemical measurements of sympathetic nervous system activity within the strains; 4) to use DNA probes specific for genes expressed in the sympathetic nervous system to identify genetic differences between strains and 5) to make these strains available to other investigators. The hypertensive strains will have a truly congenic normotensive control and will share the same genetic background themselves. Hypertensive rabbits from disparate rabbitries will be mated with rabbits from a normotensive, inbred strain (Strain III, Jackson Labs). The genes from hypertensive animals will not be mixed (as done by other investigators) in order to simplify identification of individual genetic and physiological factors causing hypertension. Blood pressure will be measured by an indirect ear artery method in F1 rabbits between 2 and 5 months of age to determine onset of hypertension. Pressure will be measured by a direct method for selection of rabbits with highest pressures to mate with controls for first backcross, N1. F1 and N1 to N4 generations of rabbits will be used also for genetic studies to determine the numbers of genes causing hypertension and to identify, by DNA probes, components of the sympathetic nervous system regulated genetically. Also studies of indices of sympathetic activity will include, in the conscious rabbit, response to a cold pressor test and reflex bradycardia during activation of arterial baroreceptors. Additionally, activities of two catecholamine synthetic enzymes will be assayed in various tissues and neuronal accumulation of norepinephrine (NE) and contractility response to NE will be assessed in blood vessels. Light and electron microscopy will be used for morphometric studies of vessels. All these studies will be evaluated with respect to levels of arterial pressure. Such data are not available in the literature at present. In summary, we shall create a tool for study of hypertension that will be of maximum usefulness to other researchers. Its outstanding virtues are: isolation in a uniform state of a sample of several different hypertensive genotypes and appropriate controls will be available for all studies since hypertensive strains are congenic with each other and with inbred normotensive strain.

该提案的目的是：1）确定和启动 遗传性高血压兔品系的发展， 共同的同类控制; 2）确定基因的数量 控制每种菌株的高血压; 3）使生理 和交感神经系统的生化测量 4）使用对菌株特异的DNA探针， 在交感神经系统中表达的基因， 菌株之间的遗传差异和5）使这些菌株 提供给其他研究者。 高血压菌株将 有一个真正的同类正常血压控制，并将分享 相同的基因背景。 高血压兔， 不同的兔子将与兔子交配， 血压正常的近交系（品系III，杰克逊实验室）。 的基因 将不混合来自高血压动物的样品（如由其他 调查员），以简化个人身份识别 引起高血压的遗传和生理因素。 血液 在F1中，将通过间接耳动脉方法测量压力 2至5个月大的兔子，以确定 高血压 将通过直接方法测量压力， 选择压力最高的家兔与对照组交配 对于第一次回交，N1。 F1和N1至N4代家兔 也将用于遗传研究，以确定 基因导致高血压，并确定，通过DNA探针， 交感神经系统的成分调节 遗传的 此外，对交感神经活动指数的研究将 包括对冷加压试验的反应 以及动脉压力感受器激活期间的反射性心动过缓。 此外，两种儿茶酚胺合成酶的活性 将在各种组织中进行测定， 去甲肾上腺素（NE）和对NE的收缩反应将是 在血管中评估。 光学和电子显微镜将是 用于血管的形态测量研究。 所有这些研究将 根据动脉压水平进行评估。 等 目前文献中没有数据。 总的来说， 我们将创建一个研究高血压的工具， 对其他研究人员最大的帮助。 其突出的美德 是：在几种不同的样品的均匀状态下分离 高血压基因型和适当的控制将是可用的 对于所有研究，因为高血压菌株与每种 其他和与近交正常血压株。