PROSTAGLANDINS, THE KIDNEY, AND HYPERTENSION

前列腺素、肾脏和高血压

• 批准号: 3336971
• 负责人: MICHAEL J DUNN
• 金额: $ 27.68万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-09-01 至 1989-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3336971
• 关键词: adenylate cyclase; adrenergic agents; angiotensin II; antihypertensive agents; calcium; gas chromatography; glomerular filtration; high performance liquid chromatography; kidney circulation; kidney metabolism; kidney transplantation; leukotrienes; mass spectrometry; nephrotic syndrome; platelet activating factor; prostaglandins; radioimmunoassay; renal glomerulus; renal hypertension; renal medulla; salt intake; thin layer chromatography; thromboxanes; tissue /cell culture; vascular resistance; vasopressins

We propose three major areas of investigation: 1) Glomerular and mesangial cell contractility will be studied using a computer-based image analysis microscopic system. We will assess the contractile effects of thromboxane A2, leukotriene C4 and D4, and platelet activating factor on isolated rat glomeruli and rat glomerular mesangial cells in culture. The glomerular contractile actions of these compounds will be blocked with specific antagonists to thromboxane receptors and leukotriene receptors. The relaxant effect of PGE2 or PGI2 will be studied and the role of intracellular cyclic AMP as the mediator of mesangial relaxation will be evaluated. The importance of calcium entry or translocation of intracellular calcium as a mediator of mesangial contraction in response to the aforementioned contractile agents will also be studied; 2) Studies of glomerular immune injury will use several models of nephrotoxic serum nephritis induced by antiglomerular basement membrane antibodies. Glomerular synthesis of leukotriene B4, C4 and D4 will be measured in normal and immune-injured glomeruli. The actions of LTC4 and LTD4 on glomerular function in vivo will be evaluated, after intrarenal infusion in the rat, with measurements of glomerular filtration rate, renal blood flow and urinary protein excretion. The therapeutic efficacy of lipoxygenase inhibitors in nephrotoxic serum nephritis will be evaluated as will the value of a leukotriene D4 receptor antagonist; 3) Renal medullary prostaglandin synthesis will be measured in salt-sensitive, hypertensive Dahl rats. Using cell culture techniques, we will determine whether reduced PGE2 synthesis is in renal medullary interstitial cells or renal papillary collecting tubular cells. Renal medullary interstitial cell synthesis of anti-hypertensive polar renomedullary lipid (platelet activating factor) will be measured and compared between hypertensive and normotensive rats. Transepithelial salt transport will be assessed in renal papillary collecting tubular cell monolayers and we will determine whether this is the site of enhanced sodium reabsorption in hypertensive salt-sensitive rats. The effects of prostaglandins and platelet activating factor on renal papillary collecting tubular cell transport will be measured.

我们提出了三个主要的研究领域：1)肾小球和系膜 将使用基于计算机的图像分析来研究细胞收缩能力 微观系统。我们将评估血栓烷的收缩效应 A_2、白三烯C_4、D_4和血小板活化因子对大鼠的影响 体外培养肾小球和大鼠肾小球系膜细胞。肾小球 这些化合物的收缩作用将被特定的 血栓烷受体和白三烯受体拮抗剂。这个 PGE2或PGI2的松弛作用将被研究，其作用 细胞内环磷酸腺苷作为系膜松弛的介体 已评估。钙离子进入或转运的重要性 细胞内钙作为肾小球系膜收缩反应的介体 还将研究上述缩宫剂；2)研究 肾小球免疫损伤将使用几种模型的肾毒性血清 抗肾小球基底膜抗体所致肾炎。 肾小球合成白三烯B4、C4和D4将在 正常肾小球和免疫受损肾小球。LTC4和LTD4在细胞上的作用 肾内输注后，将评估活体肾小球功能 测定大鼠肾小球滤过率、肾血流量 和尿蛋白排泄。脂氧合酶的疗效观察 肾毒性血清性肾炎的抑制剂将进行评估， 白三烯D4受体拮抗剂的应用价值；3)肾髓质 前列腺素合成将在盐敏感的高血压患者中进行测量 达尔大鼠。利用细胞培养技术，我们将确定 肾髓质间质细胞或肾脏合成前列腺素E_2减少 乳头状集合管细胞。肾髓质间质细胞 抗高血压极肾髓质脂类(血小板)的合成 激活因子)将在高血压和高血压之间进行测量和比较 血压正常的大鼠。跨上皮盐运输将在#年进行评估 肾乳头状收集肾小管细胞单层，我们将确定 这是否为高血压患者钠重吸收增强的部位 对盐敏感的老鼠。前列腺素与血小板活化的关系 影响肾乳头状集合管细胞转运的因素 量过了。