MINORITY SCHOOL FACULTY DEVELOPMENT AWARD

拟议研究的目标有三个：a)研究 花生四烯酸和二十碳五烯酸的长期效应 高血压大鼠(SHR)和易发卒中大鼠的血压变化 高血压大鼠(SHRSP)，b)检测离散血流动力学 慢性心力衰竭的后果(器官血流和心功能) 补充AA和EPA，c)以检查代谢和神经内分泌 长期服用AA和EPA的后果。这些目标将 通过特定的实验解决，在这些实验中，SHR、SHRSP和正常血压 将给予大鼠(S.C.)每日注射AA或EPA。血压 (BP)和心率(HR)将被跟踪3个月 尾部体积描记术和在实验结束时直接 测量下列血流动力学指标：血压、心率、心脏 输出量(CO)和离散器官血流(肾、肠系膜、 后半身)。此外，交感神经系统的活动 将通过直接测量血浆中儿茶酚胺的水平来评估 (去甲肾上腺素、肾上腺素和多巴胺)。这些目标将会实现 如下：将有意识地直接测量BP、HR和CO 老鼠。流向离散器官(肾脏、肠系膜、后肢)的血流将 通过使用VF-微探针的定向脉冲多普勒技术来完成 植入各自的动脉(麻醉下的显微手术)。 生化和内分泌状态将通过抽血进行评估 从植入股动脉的动脉中提取。儿茶酚胺会 用放免酶-薄层扫描法测定。前列腺素(PGE2， 6-酮-前列腺素F1和血栓素B2)将在血浆样本和在体外进行检测 AA和EPA处理大鼠和对照大鼠组织样本的系统 在体外孵化。这些研究将为我们提供关于 主要多不饱和脂肪降压作用机制的研究 酸(PUFA)-AA和EPA及其与前列腺素的关系 交感神经-肾上腺髓质系统。它将提供完全新的数据关于 多不饱和脂肪酸对实验性心功能和脏器血流的影响 中风和高血压的模型，最终将表明 多不饱和脂肪酸对中风的长期保护作用。自AA以来 和EPA是必需的营养素，这项研究可能支持饮食 预防或治疗过于严重的心血管疾病的方法： 中风和高血压。

The objectives of the proposed studies are threefold: a) to examine the long term effect of arachidonic acid (AA) and eicosapentaenoic acid (EPA) on blood pressure of hypertensive rats (SHR) and stroke prone spontaneously hypertensive rats (SHRSP), b) to examine the discrete hemodynamic consequences (organ blood flow and cardiac functions) of chronic supplementation of AA and EPA, c) to examine metabolic and neuroendocrine consequences of chronic AA and EPA administration. These objectives will be addressed by specific experiments in which SHR, SHRSP and normotensive rats will be given (s.c.) daily injections of AA or EPA. Blood pressure (BP) and heart rate (HR) will be followed for 3 months by tail-plethysmography and at the end of the experiments by direct measurements of the following hemodynamic measurements: BP, HR, cardiac output (CO) and discrete organ blood flow (renal, mesenteric, hindquarter). In addition, the activity of the sympathetic nervous systems will be assessed by direct measurements of plasma levels of catecholamines (norepinephrine, epinephrine and dompamine). These aims will be achieved as follows: Direct measurements of BP, HR and CO will be done in conscious rats. Blood flow to discrete organs (renal, mesenteric, hindquarters) will be done by the directional pulsed Doppler technique using VF-microprobes implanted on the respective arteries (microsurgery under anesthesia). Biochemical and endocrine status will be assessed by withdrawal of blood from arterial lines implanted in the femoral artery. Catecholamines will be assayed by the radioenzymatic-TLC method. Prostaglandins (PGE2, 6-keto-PGF1 and TXB2) will be assayed on plasma samples and in an ex-vivo system where tissue samples of AA and EPA treated and control rats are incubated in-vitro. These studies will provide new insights on the mechanism of the hypotensive effects of the major polyunsaturated fatty acid (PUFA)-AA and EPA, and its relationship to prostaglandins, and the sympatho-adrenomedullary system. It will provide absolutely new data on cardiac functions and organ blood flow response to PUFA in experimental models of stroke and hypertension and will eventually indicate the beneficial long term protective effect of PUFAs against stroke. Since AA and EPA are essential nutrients, this study might support a dietary approach to prevention or therapy of too major cardiovascular diseases: stroke and hypertension.