RENAL HUMORAL FACTORS IN RENAL FUNCTION AND HYPERTENSION

本提案的目的是确定如何 肾灌注压（RPP）的改变可以改变尿 钠排泄量（UNa）无肾血流量（RBF）变化 或肾小球滤过率。 对此负责的机制 压力相关的尿钠排泄仍然是未知的，尽管他们 在血压调节中的重要性。 从 根据我们和其他人报道的实验数据，我们提出了一个 一种假设的事件序列，通过该序列， 与RPP的变化成比例。 根据这一假设， RPP的变化引起肾素释放的负相关变化 从而参与肾内血管紧张素II（Ang II）的形成 血管紧张素II通过控制肾髓质的血流来调节肾髓质的血流。 直血管的血管张力。 髓血流量变化 引起髓体积和肾体积平行变化 间质压力改变前列腺素E2的产生 （PGE2）从肾间质细胞。 花边中的钠重吸收 近端小管或粗的上升支可由PGE2调节。 本提案将测试这一系列事件1）在狗使用 测量这些变化的传统技术 当RPP在RBF范围内或以下时， 自动调节 皮质和髓质流量和体积的变化 将使用快速X射线计算机断层扫描仪测量 系统 2)压力相关事件之间的相互作用 以及其他影响肾脏前列腺素合成的因素 髓质(i.e.渗透压、O2张力和尿素 浓度）将在犬骨髓切片中进行研究3） RPP依赖的物理因素的影响，如壁 张力和剪切力对内皮细胞释放的影响 舒张因子（EDRF）和前列环素（PGI2）将在 狗肾动脉被放置在每个物理因素 可以独立控制。 4)研究还将 进行了研究，以确定如何EDRF和PGI2产生肾 动脉节段调节肾皮质的肾素释放 切片或肾小球细胞制备物。 这些研究将 阐明肾脏调节容量的机制， 从而影响血压。

The objective of the current proposal is to determine how alterations in renal perfusion pressure (RPP) can modify urinary sodium excretion (UNa) without changes in renal blood flow (RBF) or glomerular filtration rate. The mechanisms responsible for this pressure-related natriuresis have remained unknown despite their attributed importance in the regulation of blood pressure. From experimental data reported by us and others, we have proposed a hypothetical sequence of events by which UNa is altered in proportion to changes in RPP. According to this hypothesis, changes in RPP produce inversely related changes in renin release and thereby in the intrarenal formation of angiotensin II (Ang II) Ang II modulates blood flow to the renal medulla by controlling the vascular tone of the vasa recta. Changes in medullary blood flow induce parallel changes in medullary volume and in renal interstitial pressure altering the production of prostaglandin E2 (PGE2) from renal interstitial cells. Sodium reabsorption in lace proximal tubules or thick ascending limbs may be modulated by PGE2. This proposal will test this sequence of events 1) in dogs using conventional techniques for measuring alterations in these parameters as RPP is decreased within and below the range of RBF autoregulation. Changes in cortical and medullary flow and volume will be measured using a fast x-ray computerized tomographic system. 2) The interactions between the pressure related events and other factors influencing prostaglandin synthesis in the renal medulla. (i.e. osmotic pressure, 02 tension, and urea concentration) will be investigated in canine medullary slices 3) The influence of RPP-dependent physical factors such as wall tension and shear stress, on the release of endothelia derived relaxing factors (EDRF) and prostacyclin (PGI2) will be studied in canine renal arteries placed in chambers where each physical factor can be independently controlled. 4) Studies will also be undertaken to determine how EDRF and PGI2 produced in renal arterial segments modulate the release of renin from renal cortical slices or juxtaglomerular cell preparations. These studies will elucidate the mechanisms by which the kidney regulates volume and, thereby, blood pressure.