EFFECT OF VASOACTIVE AGENTS IN THE ISOLATED GLOMERULUS

血管活性药物对孤立肾小球的影响

• 批准号: 3081822
• 负责人: TERRANCE A FRIED
• 金额: $ 6.52万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-07-01 至 1989-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3081822
• 关键词: acetylcholine; angiotensin II; bradykinin; glomerular filtration; isolation perfusion; kidney metabolism; kidney pharmacology; norepinephrine; parathyroid hormones; prostacyclins; prostaglandin E; renal glomerulus; thromboxanes; vasoactive agent; vasoconstrictors; vasodilators; vasopressins

Problem: There is a considerable amount of data in the literature which suggests that single nephron glomerular filtration rate is influenced by vasoactive hormones. These hormones include the prostaglandins, angiotensin II, norepinephrine, and vasopressin. The mechanisms by which these hormones modulate glomerular filtration have until now been investigated almost exclusively under in vivo conditions. Under these conditions, the singular effect of one hormonal manipulation is difficult to decipher due to the many systemic effects of these agents and the possible hormone-hormone interactions that may occur. Objectives: In the present project an investigation of the effects of the vasoactive agents: PGE2, PGI2, bradykinin, acetylcholine, angiotensin II, norepinephrine and vasopressin on the determinants of glomerular filtration rate (PGC, Pi GC, Kf) is proposed. A second aim of this project will be to quantify the production of TxB2, PGE, and PGI2 by a single glomerulus. Further, the response of this production to the vasoactive agents: angiotensin II, norepinephrine, and vasopressin will be measured. METHODS: The above objectives will be approached with the use of a technique recently developed in this laboratory: the isolated perfused glomerulus. This technique allows one to measure the effect of a single vasoactive compound under controlled conditions which eliminate systemic effects and minimize hormone-hormone interactions. It also allows one to measure the prostaglandin and TxB2 production by a single glomerulus under physiologic flow rates. Briefly, one dissects a single glomerulus free with intact afferent and efferent arterioles. This glomerulus which retains an intact capsule is transferred to the perfusion apparatus which utilizes two sets of pipettes: one for perfusion via the afferent arteriole as well as measurement of glomerular hydrostatic pressure and, the second, for the collection of fluid from the efferent arteriole. With this technique one can measure PGC, Pi GC, SNGFR, QA and filtration fraction and one can calculate KF.

问题：文献中有大量数据， 表明单个肾单位肾小球滤过率受 血管活性激素 这些激素包括肾上腺素， 血管紧张素II、去甲肾上腺素和加压素。 的机制 这些激素调节肾小球滤过， 几乎完全在体内条件下进行研究。 根据这些 条件下，一个荷尔蒙操纵的单一效果是困难的 由于这些药物的许多全身性作用， 可能发生的激素相互作用。 目的：在本项目中，研究了 血管活性剂：PGE2、PGI2、缓激肽、乙酰胆碱、血管紧张素II， 去甲肾上腺素和血管加压素对肾小球滤过决定因素的影响 率（PGC，Pi GC，Kf）的方法。 该项目的第二个目标是 定量单个肾小球的TxB2、PGE和PGI2的产生。 此外，这种生产对血管活性剂的反应： 将测量血管紧张素II、去甲肾上腺素和加压素。 方法：上述目标将通过使用 最近在这个实验室开发的技术：隔离灌注 肾小球 这项技术允许人们测量单个 血管活性化合物在受控条件下，消除全身 影响，并尽量减少激素的相互作用。 它还允许一个人 测量单个肾小球的前列腺素和TxB2的产生， 生理流速 简单地说，解剖单个肾小球， 有完整的传入和传出小动脉 这个肾小球 保持完整的胶囊被转移到灌注装置， 使用两套移液管：一套用于通过传入神经灌注 小动脉以及肾小球静水压力的测量， 第二，用于收集来自传出小动脉的液体。 与 该技术可以测量PGC、Pi GC、SNGFR、QA和过滤 分数和一个可以计算KF。