STRUCTURE AND FUNCTION OF CNS VESSELS IN HYPERTENSION

脑血管系统主要通过以下方式适应慢性高血压 大鼠中膜(平滑肌)过度收缩的发生 毛细血管前阻力血管和通过改变模式，密度， 大动脉的交感神经活动。我们建议 来检验这样一种假设，即这些结构性适应在大范围和 慢性高血压患者的小血管有助于正常发现 脑微血管下游的形态和功能。当地人 选定的核、束和层内的微血管供应 高血压动物大脑中的结构还没有被 用敏感的方法进行评估。这项提议的具体目标是 确定1)慢性高血压对室壁结构的影响 交感神经分布于大脑中所有连续的血管节段 脑组织光电子形态计量学，2)毛细血管血流率 不同标记小分子溶质的流动、血脑交换 物理化学性质(乙二醇、蔗糖、尿素)，以及 正常血压特定结构中微血管的血浆间隙 和高血压动物使用定量放射自显影，以及3) 在局部层面上将结构和生理信息关联起来。 我们将使用六个月大的Wistar-京都(WKY)和自发性高血压 大鼠(SHR)。大小血管的形态计量学研究将 包括长度和长度的测量，以及光滑的厚度 肌肉层。我们将定量地描述光和电子 显微水平神经-平滑肌关系与细微结构 所有血管节段的内皮细胞。这些发现将是 在可能的情况下，在个别结构内与 通过定量放射自显影获得的生理信息。所有的 这些决定将在WKY和SHR中做出，并保持完整的共鸣 神经支配和单侧交感神经支配(切除一例 一个月龄的正常颈神经节)。进一步研究 正常和正常脑血管形态和功能 单侧去神经大鼠在不同条件下，我们将重复 在我们1)产生尖锐动脉的大鼠身上进行的这些测量 2)电刺激黑质。 导致基底节高度局灶性代谢激活的程序 黑质投影场。分别，这两种操作 允许评估慢性阻塞性肺疾病患者脑血管系统的能力 高血压对机械和局部代谢刺激的反应。

The cerebrovascular system adapts to chronic hypertension primarily by development of hypertorophy of the media (smooth muscle) in the precapillary resistance vessels and by alteration of the pattern, density, and activity of the sympathetic innervation in large arteries. We propose to examine the hypothesis that these structural adaptations in large and small vessels in chronic hypertension are conducive to normal find morphology and function of downstream cerebral microvessels. The local microvascular supply within nuclei, tracts and layers of selected structures in the brains of hypertensive animals have not yet been evaluated with sensitive methods. Specific objectives of this proposal are to determine 1) the effects of chronic hypertension on the wall structure and sympathetic innervation across all consecutive vascular segments in the brain using light and electron morphometry, 2) the rate of capillary blood flow, blood-brain exchange of small labeled solutes with different physicochemical properties (ethylene glycol, sucrose, urea), and microvascular plasma space in specific selected structures of normotensive and hypertensive animals using quantitative autoradiography, and 3) correlate the structural and physiological information at the local level. We will use six month old Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). The morphometric studies of large and small vessels will include measurements of idameters and lengths, and the thickness of smooth muscle layers. We will quantitatively describe at the light and electron microscopic levels nerve-smooth muscle relationships and the fine structure of endothelial cells for all vascular segments. These findings will be correlated, within individual structures where possible, to the physiological information obtained by quantitative autoradiography. All of these determinations will be made in WKY and SHR with intact sympathetic innervation and with unilateral sympathetic denervation (removal of one superiod cervial ganglion at one month of age). To further examine cerebrovascular morphology and function in intact and unilaterally-denervation rats under different conditions, we will repeat these measurements in rats in which we 1) produce acuts arterial hypetension, and 2) electrically stimulate the substantia nigra, a procedure causing highly focal metabolic activation of basal ganglia within the field of nigral projections. Respectively, these two manipulations allow evaluation of the ability of the cerebrovascular system in chronic hypertension to respond to mechanical and local metabolic stimuli.