MICROVASCULAR ADAPTATIONS IN HYPERTENSION

5种实验动物模型微血管适应性的研究 高血压记录了不同程度的血管收缩， 小动脉管腔稀疏和结构性缩小的原因 导致外周阻力增加。目前的建议将建立在 这一基础是通过记录微血管的重建 与稀疏化相关的网络及其机制研究 导致微血管疏松。第一批实验将 记录出现在肾性高血压(1 Kg)中的任何网络变化 DOCA-盐性高血压，疗程8周。下一步的研究将测试 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-血管紧张素系统和 由于局部压力的长期变化。由此产生的其他后果 假设疏松是血管在幼年生长失败的结果。 动物的稀疏性是可逆的。这些想法将受到以下方面的检验 产生和逆转成年大鼠肾性高血压。第三 假设钠敏感的个体有高血压前期 微血管改变，这将在Spraogue-Dawley大鼠身上进行测试。 接下来，血管收缩-容量假说将直接通过 大鼠血管收缩功能和血浆肾素活性的测定 正常饮食或缺钠饮食以提高血浆肾素水平， 2肾1夹型高血压大鼠的良恶性 高血压。这些假设将在现场进行测试， 透明带光大鼠股薄肌的实验研究 氯醛糖-氨基甲酸酯。所有患者都将测量动脉血压 通过留置导管进行的终末期实验和慢性研究中 尾部手铐。微血管直径的测量将由 图像剪切闭路电视显微镜和微血管 在体内和微填充制剂中通过定量体视学测定密度。 这些研究的结果将对人类高血压产生影响。 这不仅增加了对微循环的基本了解，也增加了对疾病的认识。

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.