RENAL HUMORAL FACTORS IN RENAL FUNCTION AND HYPERTENSION

当前提案的目标是确定如何 肾灌注压(RPP)的改变可以改变尿液 钠排泄(UNA)而不改变肾血流量(RBF) 或肾小球滤过率。负责这一点的机制 与压力相关的钠尿症仍然未知，尽管他们 归因于血压调节的重要性。从… 由我们和其他人报告的实验数据，我们提出了一个 假设的事件序列，其中UNA被改变 与RPP变化的比例。根据这一假设， RPP的变化会导致肾素释放的相反相关变化 从而在肾内血管紧张素II(Ang II)的形成中 血管紧张素转换酶II通过控制血管紧张素转换酶调节肾髓质的血流 直血管的血管张力。脊髓血流量的变化 引起髓质体积和肾脏的平行变化 间质压力改变前列腺素E_2的产生 (PGE2)来自肾间质细胞。花边中的钠重吸收 近端小管或粗大的升肢可能受PGE2的调节。 这项提议将在狗身上测试这一系列事件1)使用 测量这些变化的传统技术 RPP在RBF范围内或以下时的参数 自动调节。皮质和髓质血流和体积的变化 将使用快速x射线计算机体层摄影术进行测量 系统。2)压力相关事件之间的相互作用 和其他影响肾脏前列腺素合成的因素 延髓。(即渗透压、02张力和尿素 浓度)将在犬髓切片中进行研究3) 墙等依赖于RPP的物理因素的影响 拉伸和剪切应力对内皮细胞释放的影响 松弛因子(EDRF)和前列环素(PGI2)将在 犬肾动脉放置在腔内，每个物理因素 可以独立控制。4)学习也将是 着手确定EDRF和PGI2在肾脏中是如何产生的 动脉节段调节肾皮质肾素的释放 切片或肾小球旁细胞制剂。这些研究将 阐明肾脏调节体积的机制， 因此，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.