GENETIC HYPERTENSION AND SYMPATHETIC MECHANISMS

这项建议的目的是：1)确定并开始 遗传性高血压家兔品系的研究进展 普通同源对照；2)基因数目的测定 控制各品系的高血压；3)生理性的 和交感神经系统的生化测量 菌株内的活性；4)使用针对 交感神经系统中表达的基因识别 菌株之间的遗传差异和5)使这些菌株 可供其他调查人员使用。高血压病毒株会 有一个真正的同源正常血压控制，并将分享 具有相同的遗传背景。高血压兔来自 不同的兔子将与来自一个国家的兔子杂交 血压正常的近交系(品系III，杰克逊实验室)。基因 来自高血压动物的不会混合(如由其他 调查人员)，以简化个人身份识别 引起高血压的遗传和生理因素。血样 F1将采用间接耳动脉法测量血压 2至5个月龄兔确定发病情况 高血压。压力将通过直接方法测量 选择压力最高的兔与对照组交配 对于第一个回交，N1。兔的F1和N1~N4代 也将被用于基因研究，以确定 导致高血压的基因，并通过DNA探针识别， 交感神经系统的组成成分受到调节 从基因上来说。交感神经活动指数的研究也将 在清醒的兔子中包括对冷加压试验的反应 动脉压力感受器激活时出现反射性心动过缓。 此外，两种儿茶酚胺合成酶的活性 会在不同的组织和神经元中积聚 去甲肾上腺素(NE)及对NE的收缩反应 在血管中进行评估。光学和电子显微镜将是 用于血管的形态测量研究。所有这些研究都将 根据动脉压水平进行评估。是这样的 目前还没有文献中的数据。总而言之， 我们将创建一个研究高血压的工具，它将是 对其他研究人员的最大用处。它的突出优点 主要有：隔离在均匀状态下的几种不同的样品 将提供高血压基因分型和适当的对照。 用于所有研究，因为高血压病毒株是同源的 其他与近亲交配的正常血压品系。

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.