RENAL MEDULLARY FUNCTION AND ARTERIAL PRESSURE CONTROL

肾髓质功能和动脉压控制

• 批准号: 3736368
• 负责人: ALLEN W COWLEY
• 金额: --
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3736368
• 关键词: angiotensin II; blood pressure; blood volume; bradykinin; captopril; cardiac output; computer simulation; disease /disorder model; hormone regulation /control mechanism; kidney circulation; kidney function; kidney pharmacology; laboratory rat; mathematical model; microcirculation; nitric oxide; norepinephrine; renal hypertension; renal medulla; saluresis; spontaneous hypertensive rat; ultrasound blood flow measurement; vascular smooth muscle; vasoactive agent

The proposed studies will determine if the renal medulla plays an important role in determining the long-term level of arterial blood pressure. We will chronically reduce papillary blood flow to see if this leads to hypertension and chronically elevate papillary flow to see if this leads to hypotension. Two new techniques were necessary and are used for these studies. One, implanted medullary interstitial catheters to target delivery of substances into the renal medulla, acutely and chronically. The other, acute and chronically implanted optical fibers in the renal cortex, outer and inner medulla for measurement of changes in regional blood flow using laser-Doppler flowmetry. These techniques have been designed to be performed in conscious rats and at this time can be used reliably for periods exceeding 3 weeks. One series of studies is designed to determine the acute effects of renal medullary interstitial infusions of vasoconstrictors and dilators which alter papillary blood flow will produce chronic alterations of arterial pressure. A third series of studies will determine if chronic medullary interstitial infusion of compounds that increase papillary blood flow in SHR can reset the pressure-natriuretic relationship and normalize arterial pressure. Positive findings would support the concept that subtle changes in medullary function may precede global changes in renal function and may be an important initiating element in the etiology of hypertension.

这项研究将确定肾髓质是否在肾脏中起着重要作用。 在确定动脉血的长期水平中的重要作用 压力 我们将长期减少乳头状血流量， 这导致高血压和慢性升高乳头状血流， 如果这导致低血压。 两种新技术是必要的， 用于这些研究。 一种是植入骨髓间质导管 以将物质靶向递送到肾髓质中， 长期地。 另一种是急性和慢性植入的光纤 在肾皮质、外髓质和内髓质中测量变化 用激光多普勒血流仪测量局部血流。 这些技术 被设计成在有意识的老鼠身上进行， 可以可靠地使用超过3周的时间。 一个系列的 研究旨在确定肾髓质的急性效应， 血管收缩剂和扩张剂的间质输注， 乳头状血流将产生动脉的慢性改变， 压力 第三个系列的研究将确定慢性骨髓炎是否 增加乳头状血流量的化合物的间质输注 SHR可以重置血压-利钠关系， 动脉压 积极的调查结果将支持以下概念， 髓质功能的细微变化可能先于肾功能的整体变化。 功能，并可能是一个重要的启动因素的病因学 高血压