MACULA DENSA CONTROL OF FILTRATION AND RENIN RELEASE

黄斑致密层对过滤和肾素释放的控制

• 批准号: 3236355
• 负责人: JURGEN SCHNERMANN
• 金额: $ 14.21万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-07-01 至 1991-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3236355
• 关键词: glomerular filtration; hormone regulation /control mechanism; juxtaglomerular apparatus; laboratory rabbit; laboratory rat; micropuncture; peptidases; renal tubular transport; renin; sodium chloride; vasoconstrictors; vasodilators

The juxtaglomerular apparatus links the glomerulus, where plasma undergoes filtration to form primary urine, and a late nephron site at which tubular fluid is markedly reduced in volume and concentration by tubular absorption. By detecting changes in fluid composition the tubular cells at the contact point, the macula densa cells, are able to receive and transmit a message that affects the rate of filtration in the glomerulus. Increases in NaCl concentration depress filtration rate. Thus, the juxtaglomerular apparatus serves to stabilize the concentration of NaCl entering the distal portions of the nephron by negative feedback coupling. The precise relation between the tubular signal and filtration rate (and therefore the regulatory potential of this feedback system) is variable with tight coupling in states of dehydration and loose coupling in states of extracellular volume expansion. A special cell population within the juxtaglomerular apparatus, the granular cells, is the site of synthesis of renin, the proteolytic enzyme involved in the generation of angiotensin II. Release of renin is controlled in part by distal tubule fluid composition using the macula densa-granule cell pathway. Thus, the macula densa serves two functions in the control of body fluid volumes, regulation of distal nephron NaCl delivery and control of plasma angiotensin concentration, a hormone with multiple effects on Na balance. Experiments will be carried out to develop a better understanding of the mechanisms causing the change in the relationship between the macula densa signal and filtration rate and its functional consequences and to define the relation between the dual role of the macula densa as a controller of filtration rate on the one hand and of renin release on the other. Studies will use a combination of micropuncture and isolated perfused tubule methods for study of single nephron function, and will utilize a recently developed ultra-micro renin assay method that permits accurate measurement of single nephron renin release. The following general propositions will be tested experimentally: 1) the macula densa mediated changes in filtration rate and renin secretion are initiated by identical cellular responses to a luminal signal. 2) the sensitivity of the macula densa mechanism for filtration rate control is affected by the net balance of vasodilator and vasoconstrictor influences prevailing at a given time and does not reflect a primary alteration in intrinsic function of the juxtaglomerular apparatus.

肾小球体连接肾小球，血浆在肾小球中经历 过滤以形成初级尿，以及晚期肾单位部位，在该晚期肾单位部位， 液体的体积和浓度明显减少， 吸收 通过检测液体成分的变化， 接触点，即致密斑细胞，能够接收和传输 影响肾小球滤过率的信息。 增加 NaCl浓度降低了过滤速率。 因此，肾小球 装置用于稳定进入远端的NaCl浓度， 部分肾单位的负反馈耦合。 的精确 肾小管信号和滤过率之间的关系（因此 该反馈系统的调节潜力）随紧度而变化。 脱水状态下的耦合和 细胞外容积扩张 一种特殊的细胞群， 肾小球器，颗粒细胞，是合成 肾素，参与血管紧张素生成的蛋白水解酶 二. 肾素的释放部分受远端小管液的控制 使用致密斑-颗粒细胞途径来制备组合物。 因此，黄斑 densa在控制体液量、调节 远端肾单位NaCl输送和血浆血管紧张素 浓度，一种对钠平衡有多种影响的激素。 实验 将开展一项活动，以更好地了解 引起致密斑信号和 过滤速率及其功能后果，并定义关系 致密斑作为过滤控制器的双重作用 另一方面是释放的速度。 研究将使用 显微穿刺和离体灌流小管联合法研究 单肾单位功能，并将利用最近开发的 一种能精确测定单个 肾单位肾素释放。 下面的一般命题将被测试 实验上：1）致密斑介导的滤过率变化 和肾素分泌是由相同的细胞反应启动的， 管腔信号 2)致密斑机制的敏感性 滤过率控制受血管扩张剂的净平衡影响， 血管收缩剂的影响在给定的时间普遍存在，并不反映 肾小球体内在功能的一种主要改变。