THROMBOXANE IN SEVERE HYPERTENSION

易卒中亚系自发性高血压大鼠(SHRSP) 出现严重的高血压、肾功能障碍、脑血管病变和 卒中。我们发现慢性血管紧张素转换疗法 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，即使血液 压力并没有大幅降低。脑组织学检查 用血管紧张素转换酶抑制剂治疗的SHRSP患者的肾脏没有证据表明 未经治疗的SHRSP患者出现严重的脑血管和肾脏损害。 该项目的目的是确定ACE的效果 SHRSP中预防中风和肾功能障碍的抑制剂是 肾素-血管紧张素系统(RAS)的表达变化。时间- RAS组件的相关更改将在 出现严重高血压、肾功能障碍和中风。代理 干扰血管紧张素II的形成或阻断其作用 (Ang II)将用于确定这些制剂是否会改变 发生中风、肾功能不全和严重高血压。这个 还将在下列条件下检查AGE抑制剂的作用 严重高血压与血管紧张素Ⅱ(Ang II- 诱发性高血压)或Ang II水平降低(DOCA-盐性高血压)。 血管紧张素转换酶抑制剂对预防中风和肾脏的作用 功能障碍是组织血管紧张素转换酶表达的抑制也会 检查过了。组织血管紧张素转换酶抑制作用的剂量依赖性和时间依赖性 血管紧张素转换酶抑制剂逆转组织血管紧张素转换酶抑制的依赖性 撤除治疗将与心力衰竭的病理生理变化相关。 加盐的SHRSP。血管紧张素转换酶抑制剂的有益作用 治疗与盐负荷后血压升高的变化有关 SHRSP将在ACE抑制剂治疗的研究中进行检查 开始于严重高血压的早期或晚期。 其他降压药将作为阳性同时给药 对照以确定肾功能是否幸免，卒中是否减轻为 血压变化的结果。中风是目前全国最严重的 第三大杀手(每年超过15万美国人)。我们的研究将 提供与治疗有关的领域的重要信息 高血压、肾功能障碍和中风。

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inhibition of tissue ACE and the time dependence for reversal of tissue ACE inhibition after ACE inhibitor treatment is withdrawn will correlated with pathophysiologic changes in salt-loaded SHRSP.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.