MINORITY SCHOOL FACULTY DEVELOPMENT AWARD

拟议研究的目标有三个方面： 花生四烯酸（AA）和二十碳五烯酸（EPA）的长期作用 对高血压大鼠（SHR）和自发性脑卒中易感大鼠血压的影响 高血压大鼠（SHRSP），B）检查离散血流动力学 慢性心脏病的后果（器官血流和心脏功能） 补充AA和EPA，c）检查代谢和神经内分泌 慢性AA和EPA管理的后果。 这些目标将 通过特定的实验来解决，在这些实验中，SHR、SHRSP和血压正常的 将给予大鼠（s.c.）每天注射AA或EPA。 血压 (BP)和心率（HR）将随访3个月， 尾体积描记法和在实验结束时通过直接 测量以下血流动力学测量值：BP、HR、心脏 输出（CO）和离散器官血流（肾，肠系膜， hindquarter）。 此外，交感神经系统的活动 将通过直接测量血浆儿茶酚胺水平进行评估 （去甲肾上腺素、肾上腺素和多巴酚丁胺）。 这些目标将会实现 如下所示：BP、HR和CO的直接测量将在有意识的情况下进行 大鼠 流向离散器官（肾脏、肠系膜、后肢）的血液将 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）。 将通过抽血评估生化和内分泌状态 从植入股动脉的动脉管路中取出。 儿茶酚胺会 用放射酶-薄层色谱法测定。 前列腺素（PGE 2， 6-酮-PGF 1和TXB 2）将在血浆样品和离体样品中进行测定。 系统，其中AA和EPA处理的大鼠和对照大鼠的组织样品 体外孵育。 这些研究将提供新的见解 主要多不饱和脂肪酸的消肿作用机理 酸（PUFA）-AA和EPA，及其与拟南芥素的关系， 交感肾上腺髓质系统 它将提供绝对新的数据， 多不饱和脂肪酸对实验性大鼠心功能和器官血流的影响 中风和高血压的模型，并将最终表明 PUFA对中风的有益长期保护作用。 自AA以来 和EPA是必需的营养素，这项研究可能支持饮食 预防或治疗重大心血管疾病的方法： 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.