STRUCTURE AND FUNCTION OF CNS VESSELS IN HYPERTENSION

脑血管系统适应慢性高血压主要是通过 中膜（平滑肌）肥厚的发展 毛细血管前阻力血管和改变的模式，密度， 和大动脉中交感神经支配的活性。 我们提出 为了检验这些结构适应性在大范围内， 慢性高血压小血管有助于正常发现 下游脑微血管的形态和功能。 当地 微血管供应的细胞核，束和层选择 高血压动物大脑中的结构尚未被发现。 用敏感的方法进行评估。 这项建议的具体目标是 确定1）慢性高血压对室壁结构的影响 和交感神经支配在所有连续的血管节段， 光镜和电镜观察脑组织形态学改变; 2）毛细血管血流量 流动，血脑交换的小标记的溶质与不同的 理化性质（乙二醇、蔗糖、尿素），以及 血压正常的特定结构中的微血管血浆空间 和高血压动物使用定量放射自显影，和3） 在局部水平上将结构和生理信息关联起来。 我们将使用六个月大的Wistar-Kyoto（WKY）和自发性高血压患者。 大鼠（SHR）。 大小血管的形态计量学研究将 包括测量的idameters和长度，和光滑的厚度 肌肉层 我们将定量地描述光和电子 微观水平神经-平滑肌关系和精细结构 所有血管段的内皮细胞。 这些发现将是 在可能的情况下，在各个结构内与 通过定量放射自显影术获得的生理信息。 所有 这些测定将在交感神经完整的WKY和SHR中进行 神经支配和单侧交感神经去支配（去除一个 1月龄时的颈神经节上膜）。 进一步探讨在 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 这些测量在大鼠中，我们1）产生急性动脉炎， 高血压，和2）电刺激黑质， 导致基底神经节高度局灶性代谢活化的手术 黑猩猩的投射领域 这两种手法 允许评估慢性脑血管疾病患者的脑血管系统能力， 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.