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: 3236353
• 负责人: JURGEN SCHNERMANN
• 金额: $ 13.24万
• 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/3236353
• 关键词: glomerular filtration; hormone regulation /control mechanism; juxtaglomerular apparatus; 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.

肾小球旁结构连接肾小球，血浆在肾小球内 滤过以形成初级尿液，以及肾小管的晚期肾单位部位 液体的体积和浓度通过管状结构显著减少 吸收。通过检测液体成分的变化，肾小管细胞 接触点，致密斑细胞，能够接收和发送 影响肾小球滤过率的信息。增加 在氯化钠浓度下，会降低过滤速度。因此，肾小球旁 用于稳定进入远端的氯化钠浓度的装置 部分肾单位通过负反馈耦合。精准的 管状信号和滤过率之间的关系(因此 该反馈系统的调节潜力)随TECH而变化 脱水态的偶合和疏松的偶合 细胞外体积扩张。一种特殊的细胞群体 肾小球旁器，即颗粒细胞，是合成 肾素，参与血管紧张素生成的蛋白水解酶 II.肾素的释放部分由远端小管液控制 成分采用致密斑-颗粒细胞通路。因此，黄斑 Densa在控制体液容量、调节 远端肾单位氯化钠输送与血浆血管紧张素的控制 浓度，一种对钠平衡有多种影响的激素。实验 将开展工作，以更好地了解这些机制 导致致密黄斑信号和致密黄斑信号之间的关系改变 滤速及其功能后果及其关系的界定 在致密黄斑作为滤过控制器的双重作用之间 一方面是肾素的释放，另一方面是肾素的释放。研究将使用 显微穿刺法与离体灌流管相结合的研究 单肾单位的功能，并将利用最近开发的 超微量肾素测定法，可准确测量单个肾素 肾单位肾素释放。我们将测试以下一般性命题 实验方面：1)致密黄斑介导了滤过率的变化。 和肾素分泌是由相同的细胞反应启动的 流明信号。2)致密黄斑机制对 滤过率的控制受血管扩张剂和 血管收缩作用在给定时间占优势，并不反映 肾小球旁结构固有功能的主要改变。