MICROVASCULAR ALTERATIONS IN HYPERTENSION

微血管在发育过程中发生形态学变化， 高血压 小动脉壁增厚， 在高血压动物中已经报道了一些特定的血管， 人类 对体液因子的敏感性也可能增加。 的 这些变化对毛细血管液体交换、 血液流动，高血压的发展和维持 开始被探索。 我们建议使用直接微循环 股薄肌和肠系膜血管床的技术，包括： 活体荧光显微镜血管定量体视学 长度和表面积密度，血管的电视显微镜检查 直径和壁/腔比，双缝红细胞速度 光度法、伺服零位微压及其应用 血管活性剂与微量移液器，研究微循环 在几种大鼠高血压模型的发展过程中的动力学。 将在SHR中进行微血管改变的纵向研究， 1-肾-1-夹、1-肾-1-夹、DOCA-盐和Dahl高血压大鼠。 确定神经和局部/体液的相对影响 机制，将在3个连续状态下进行测量，受神经支配， 去神经和血管舒张。 5个模型的比较将涉及 负责结构变化的机制以及决定 结构改变是否是特定类型的 高血压，或共同分享。 微血管压力曲线和红色 细胞速度数据将添加生理信息， 观察到形态学改变。 各种抗高血压药物将 长期和急性使用，以确定导致 微血管改变 对去甲肾上腺素、血管紧张素II敏感 和加压素将通过直接应用于 用微量移液器的微容器。 的功能意义 微血管的改变将通过研究运动 充血、反应性充血和微血管的肌源性反应， 这些高血压模型。 这些研究将提供信息， 评估微循环的结构变化，并确定 它们在高血压中的病因、作用和功能意义。

Morphological changes occur in microvessels during development of hypertension. Thickening of arteriolar walls and alterations in actual number of certain vessels have been reported in hypertensive animals and humans. Sensitivity to humoral agents also may be increased. The implication of these changes for capillary fluid exchange, regulation of blood flow, and development and maintenance of hypertension are just beginning to be explored. We propose to use direct microcirculatory techniques on gracilis muscle and mesenteric vascular beds, including: in vivo quantitative stereology using intravital fluoromicroscopy for vessel length and surface area densities, television microscopy for vessel diameters and wall/lumen ratios, red cell velocity by the dual-slit photometric method, servo-null micropressures, and application of vasoactive agents with micropipettes, to investigate microcirculatory dynamics during development of hypertension in several rat models. Longitudinal studies of the microvascular alterations will be made in SHR, 1-kidney-1-clip, 1-kidney-1-clip, DOCA-salt, and Dahl hypertensive rats. To determine the relative influence of neural, and local/humoral mechanisms, measurements will be made in 3 consecutive states, innervated, denervated, and vasodilated. Comparison of the 5 models will implicate mechanisms responsible for the structural changes as well as determine whether structural alterations are specific to a certain type of hypertension, or commonly shared. Microvascular pressure profiles and red cell velocity data will add physiological information to correlate with observed morphological alterations. Various antihypertensive agents will be used chronically and acutely to determine the mechanisms leading to the microvascular alterations. Sensitivity to norepinephrine, angiotensinII and vasopressin will be determined by direct application to the microvessels with micropipettes. The functional significance of microvascular alterations will be investigated by studying exercise hyperemia, reactive hyperemia, and myogenic responses of microvessels in these hypertensive models. These studies will provide information to assess structural alterations in the microcirculation and to determine their cause, role, and functional significance in hypertension.