PREVENTION OF STROKE & KIDNEY DYSFUNCTION

易卒中亚系自发性高血压大鼠（SHRSP） 出现严重高血压、肾功能不全、脑血管病变， 中风我们发现血管紧张素转换酶的长期治疗 酶（ACE）抑制剂依那普利和卡托普利维持肾功能 显著提高了饮用盐水的SHRSP的存活率， 压力基本上没有降低。脑组织学检查 用ACE抑制剂治疗的SHRSP的肾脏没有显示出 未治疗的SHRSP中观察到严重的脑血管和肾脏病变。 本项目的目的是确定ACE的效果是否 抑制剂，以防止中风和肾功能障碍的SHRSP是 在肾素-血管紧张素系统（RAS）的变化的表达。时间- RAS组件的相关更改将在 严重高血压、肾功能不全和中风的发展。剂 干扰血管紧张素II的形成或阻断其作用 (ANG II）将用于确定这些代理是否改变 发生脑卒中、肾功能不全和严重高血压。的 AGE抑制剂的作用也将在以下条件下进行检查， 严重的高血压与血管紧张素II（ANG II-）水平升高有关。 诱导的高血压）或降低的ANG II水平（DOCA-盐高血压）。 ACE抑制剂预防中风和肾脏损害的作用 功能障碍是组织ACE抑制的一种表达， 考察组织ACE抑制的剂量依赖性和时间依赖性 ACE抑制剂后逆转组织ACE抑制的依赖性 停止治疗将与以下病理生理变化相关： 含盐SHRSP。ACE抑制剂的有益作用是否 治疗涉及盐负荷的血压升高的改变 SHRSP将在ACE抑制剂治疗为 在严重高血压发展的早期或晚期开始。 其他抗高血压药物将作为阳性合并用药 对照，以确定肾功能是否保留，卒中是否减少， 这是血压变化的结果。中风是目前全国 第三大杀手（每年超过15万美国人）。我们的研究将 在与治疗相关的领域提供重要信息 高血压、肾功能不全和中风。

Spontaneously hypertensive rats of the stroke-prone substrain (SHRSP) develop severe hypertension, renal dysfunction, cerebrovascular lesions and stroke. We have found that chronic therapy with the angiotensin-converting enzyme (ACE) inhibitors enalapril and captopril maintained kidney function and markedly improved survival of saline-drinking SHRSP even though blood pressure was not substantially lowered. Histological examination of brains and kidneys from SHRSP treated with ACE inhibitors revealed no evidence of the severe cerebrovascular and renal lesions observed in untreated SHRSP. The aim of this project is to determine whether the effect of ACE inhibitors to prevent stroke and kidney dysfunction in SHRSP is the expression of alterations in the renin-angiotensin system (RAS). Time- related changes in components of the RAS will be determined during the development of severe hypertension, renal dysfunction and stroke. Agents that interfere with the formation or block the actions of angiotensin II (ANG II) will be used to establish whether these agents alter the occurrence of stroke, renal dysfunction and severe hypertension. The actions of AGE inhibitors will also be examined under conditions in which severe hypertension is associated with elevated levels of ANG II (ANG II- induced hypertension) or reduced levels of ANG II (DOCA-salt hypertension). Whether the effect of ACE inhibitors to prevents stroke and kidney dysfunction is an expression of inhibition of tissue ACE will also be examined. The dose dependence for inhibition of tissue ACE and the time dependence for reversal of tissue ACE inhibition after ACE inhibitor treatment is withdrawn will correlated with pathophysiologic changes in salt-loaded SHRSP. Whether the beneficial effects of ACE inhibitor treatment relates to alterations in blood pressure elevation of salt-loaded SHRSP will be examined in studies in which ACE inhibitor therapy is commenced early or late in development of severe hypertension. Other antihypertensive agents will be administered as positive concurrent controls to determine if renal function is spared and stroke diminished as a result of alterations in blood pressure. Stroke is currently the nation's third largest killer (over 150,000 Americans/year). Our studies will provide important information in an area relevant to the therapy of hypertension, kidney dysfunction and stroke.