HORMONAL INFLUENCES ON THE RENAL MICROVASCULATURE

血管紧张素II（ANGII）可通过作用引起肾血管收缩， 传入（AFF）和传出（EFF）小动脉;然而，这些 血管收缩反应在体内和体外都是不稳定表达的。 体外，表明一些定义不明确的因素决定是否 血管紧张素Ⅱ在肾小球前和/或肾小球后部位引起血管收缩。 的 该项目的总体目标是提供具体信息 关于ANGII影响肾脏的机制， 微血管阻力 该项目由两个一般领域组成 强调。 第一部分是综合因素分析 这可能会影响血管紧张素Ⅱ的血管收缩作用， 肾微血管网的特定节段。 体外 血液灌注延髓肾单位技术将被开发用于 实现直接的微血管通路，同时保留解剖结构和 肾小管和血管成分之间的功能相互关系 肾血管单位 我们将确定AFF和 EFF对ANGII的反应受到以下物质的调节作用的影响 内皮源性舒张因子（EDRF）。 我们还将确定 外髓直降血管阻力的贡献 血管紧张素II和精氨酸的肾小球后作用的改变 加压素 我们将研究这些肽改变DVR的能力， 直径，直接或继发于动脉的小动脉效应， 药物，并将评估花生四烯酸的调节作用 代谢产物和EDRF。 第二个重点领域涉及 表征由ANGII诱发的细胞内信号传导事件， 检验AFF和EFF小动脉不同的假设 网站. 将在体外研究分离的AFF和EFF小动脉， 允许对直径响应进行视频测量监测， 胞内离子激发波长荧光分析 浓度和膜电位。 我们将决定 AFF和EFF小动脉对ANGII的反应在Ca 2+方面不同 进入要求，去极化的作用和起源，以及 IP 3和蛋白激酶C依赖的过程。 预计各国 这些研究将揭示功能相关的区别， 血管紧张素Ⅱ对肾小球前和肾小球后血管的影响的决定因素 部分，以及提供有关激素的进一步信息 在调节血管阻力的相互作用，通过离散 肾脏微循环网络的部分。

Angiotensin II (ANGII) can elicit renal vasoconstriction through effects on both afferent (AFF) and efferent (EFF) arterioles; however, these vasoconstrictor responses are variably expressed both in vivo and in vitro, indicating that some poorly-defined factor(s) determine whether ANGII elicits vasoconstriction at pre-and/or postglomerular sites. The overall goal of this project is to provide specific information regarding the mechanisms through which ANGII influences renal microvascular resistance. The project is comprised of two general areas of emphasis. The first involves an analysis of integrative factors which might influence the vasoconstrictive influence of ANGII on specific segments of the renal microvascular network. The in vitro blood-perfused juxtamedullary nephron technique will be exploited to achieve direct microvascular access while preserving the anatomical and functional interrelationships between tubular and vascular components of the nephrovascular unit. We will determine the extent to which AFF and EFF responses to ANGII are influenced by the modulatory effects of endothelium-derived relaxing factor (EDRF). We will also determine the contribution of outer medullary descending vasa recta (DVR) resistance alteration to the postglomerular actions of ANGII and arginine vasopressin. We will examine the ability of these peptides to alter DVR diameter, either directly or secondary to the arteriolar effects of the agents, and will assess the modulatory influences of arachidonic acid metabolites and EDRF at this site. The second area of emphasis involves characterization of intracellular signaling events evoked by ANGII, testing the hypothesis that these differ at AFF and EFF arteriolar sites. Isolated AFF and EFF arterioles will be studied in vitro, allowing videometric monitoring of diameter responses as well as dual excitation wavelength spectrofluorometric analysis of intracellular ion concentrations and membrane potential. We will determine whether or not AFF and EFF arteriolar responses to ANGII differ with regard to Ca2+ entry requirements, the role and origin of depolarization, and the roles of IP3-and protein kinase C-dependent processes. It is anticipated that these studies will reveal functionally relevant distinctions between the determinants of ANGII's effects on pre-and postglomerular vascular segments, as well as providing further information regarding hormonal interactions in the regulation of vascular resistance by discrete segments of the renal microcirculatory network.