BRADYKININ VASCULAR INFLUENCE AND ACE INHIBITION

激肽释放酶-激肽系统的作用及其与血管内皮细胞的相互作用 肾脏中的肾素-血管紧张素系统及其对作用的贡献 血管紧张素转换酶（ACE）抑制剂的作用机制尚不清楚。 通过使用药物阻断激肽释放酶-激肽系统 与血管紧张素II（All）拮抗剂，我们将确定的影响， 激肽对血压（BP）、肾血流量（RBF）、GFR、尿流量和 麻醉家兔的钠和钾排泄。这些参数 将在基础条件下和ACE抑制期间测量。激肽 将在钠限制、钠 补充剂和三种形式的高血压。急性和 ACE抑制剂的长期应用将根据这些不同的检查 条件据推测，有一个相互作用之间的 肾素-血管紧张素系统和激肽释放酶-激肽系统。通过分析 当这些系统被激活时，激肽和AH会参与血管， 我们将通过这些来获得关于血压和血流调节的信息， 肽激素将通过电流量计监测BP和RBF， 测定血浆肾素活性，以及缓激肽拮抗剂的作用， DArg（Hyp 3，DPhe 7）缓激肽（NPY 567）和新的非肽类A11拮抗剂 (DUP 753）或saralasin测定BP、RBF、肾功能和 对ACE抑制剂的反应。在确定了激肽在 这些参数在体内，更详细的研究因素的调节 将追踪肾激肽释放和代谢。一种新的制剂， 在本实验室中开发的兔肾内动脉网络将 被利用。首先，活性激肽释放酶和前激肽释放酶将被确定 在来自钠限制和 补充动物，以及低和高肾素高血压。第二、 动脉网络将被灌注和灌流以允许确定 血管腔内和外腔部位释放激肽。如何所有 拮抗剂、ACE抑制剂、β-肾上腺素受体激动剂和拮抗剂，和 激肽代谢抑制剂影响肾动脉释放激肽 将提供一个更好的了解激肽的作用，在正常的肾脏 以及高血压的影响。

The role of the kallikrein-kinin system and its interaction with the renin-angiotensin system in the kidney and its contribution to the effect of angiotensin converting enzyme (ACE) inhibitors is not well understood. Through the use of agents that block the kallikrein-kinin system together with angiotensin II (All) antagonists, we will determine the influence of kinins on blood pressure (BP), renal blood flow (RBF), GFR, urine flow, and sodium and potassium excretion in the anesthetized rabbit. These parameters will be measured under basal conditions and during inhibition of ACE. Kinin influence will be contrasted under conditions of sodium restriction, sodium supplementation and in three forms of hypertension. Both the acute and chronic application of ACE inhibitors will be examined under these various conditions. It is hypothesized that there is an interaction between the renin-angiotensin system and the kallikrein-kinin system. By analyzing the vascular participation of kinins and AH when these systems are activated, we will gain information about BP and blood flow regulation by these peptide hormones. BP and RBF, by electroflowmetry, will be monitored, plasma renin activity determined, and the effects of bradykinin antagonist, DArg(Hyp3,DPhe7) bradykinin (NPY 567) and new nonpeptide All antagonist (DUP 753) or saralasin determined on BP, RBF, renal function and the response to an ACE inhibitor. After establishing the role of kinins on these parameters In Vivo, more detailed studies on the factors regulating renal kinin release and metabolism will be pursued. A novel preparation of the rabbit intrarenal arterial network developed in this laboratory will be utilized. First, active kallikrein and prekallikrein will be determined in a microsomal fraction of intrarenal arteries from sodium restricted and supplemented animals, and from low and high renin hypertensives. Secondly, the arterial network will be perfused and superfused to allow determination of kinin release from the vascular lumenal and ablumen sites. How AII antagonists, ACE inhibitor, beta-adrenoceptor agonist and antagonist, and inhibitors of kinin metabolism affect kinin release from the renal arteries will provide a better understanding of the kinin role in the normal kidney and that affected by hypertension.