MICROVASCULAR ADAPTATIONS IN HYPERTENSION

五种实验性肝硬化模型微血管适应性的观察 高血压已经证实了不同程度的血管收缩， 小动脉管腔尺寸的稀疏和结构性减小 外周阻力增加 目前的建议将建立在 通过记录微血管的重组， 网络与稀疏和调查的机制 导致微血管稀疏 第一批实验将 记录肾性高血压（1 KG）中出现的任何网络变化， 持续8周的DOCA盐高血压。 接下来的研究将测试 假设微血管密度的变化提供了一种机制， 血液流动的长期自动调节。 这将通过实验来检验 交感神经、肾素-血管紧张素系统的作用， 由于局部压力的长期变化。 这件事的其他后果 有一种假说认为，血管稀疏是年轻人血管生长失败 动物，而且稀疏化是可逆的。 这些想法将由 在成年大鼠中产生并逆转肾性高血压。 第三 假设钠敏感个体有高血压前期 微血管改变，这将在Sprague-Dawley大鼠中进行测试。 接下来，血管收缩-容积假说将通过以下方法直接检验： 在1 KG时测量血管收缩和血浆肾素活性， 正常饮食或缺钠饮食以增加血浆肾素水平， 两肾一夹高血压大鼠的良性和恶性 高血压 这些假设将在现场进行测试， 麻醉大鼠股薄肌透照 氯醛糖尿烷。 将测量所有患者的动脉血压 通过留置导管进行的终末实验和 尾铐 将通过以下方法测量微血管直径： 图像剪切闭路电视显微镜和微血管 通过定量体视学在体内和Microfill制剂中测定密度。 这些研究的结果将对人类高血压有意义 疾病以及增加对微循环的基本了解。

A survey of microvascular adaptatations in 5 models of experimental hypertension has documented various degrees of vasoconstriction, rarefaction and structural reductions in arteriolar lumen size contributing to increased peripheral resistance. The present proposal will build on this foundation by documenting the restructuring of the microvascular network associated with rarefaction and investigating the mechanisms responsible for microvascular rarefaction. The first experiments will document any network changes that appear in renal hypertension (1KG) and DOCA-salt hypertension of 8 weeks duration. The next studies will test the hypothesis that changes in microvascular density provide a mechanism for long-term autoregulation of blood flow. This will be tested by experiments on the role of the sympathetic nerves, the renin-angiotension system, and by chronic variations in local pressure. Other ramifications of this hypothesis are that rarefaction is a failure of vessels to grow in young animals and that rarefaction is reversible. These ideas will be tested by producing and reversing renal hypertension in adult rats. The third hypothesis is that sodium sensitive individuals have prehypertensive microvascular alterations and this will be tested in Sprague-Dawley rats. Next, the vasoconstriction-volume hypothesis will be tested directly by measurements of vasoconstriction and plasma renin activity in 1KG on either a normal diet or a sodium deficient diet to increase plasma renin levels, and in 2-kidney-1-clip hypertensive rats with benign and malignant hypertension. These hypotheses will be tested in the in situ, transilluminated gracilis muscle of rats anesthetized with chloralose-urethane. Arterial blood pressure will be measured in all terminal experiments through indwelling catheters and in chronic studies by tail cuff. Measurements will be made of microvessel diameters by image-shearing closed circuit television microscopy, and microvessel density by quantitative stereology in vivo and in Microfill preparations. Results of these studies will have implications for human hypertensive disease as well as add to the basic understanding of the microcirculation.