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 在传入(AFF)和传出(EFF)小动脉上；然而，这些 血管收缩反应在体内和体内都有不同的表达 体外，表明一些定义不清的因素(S)决定了 血管紧张素转换酶在肾小球前和/或肾小球后部位引起血管收缩。这个 该项目的总体目标是提供具体的信息 关于血管紧张素转换酶影响肾脏的机制 微血管阻力。该项目由两个大体区域组成 重要的是。第一，综合因素的分析。 可能影响血管紧张素Ⅱ对血管的收缩作用 肾微血管网络的特定节段。试管苗 将利用血液灌流延髓旁肾单位技术 实现直接的微血管通路，同时保留解剖和 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 血管紧张素转换酶对血管紧张素转换酶的调节作用 内皮源性松弛因子(EDRF)。我们还将确定 延髓外段直肠降支阻力的作用 血管紧张素转换酶和精氨酸对肾小球后活动的影响 加压素。我们将研究这些多肽改变DVR的能力 直径，直接或继发于小动脉的影响 药物，并将评估花生四烯酸的调节影响 这个部位的代谢物和EDRF。第二个重点领域涉及 血管紧张素转换酶激活的细胞内信号事件的特征， 检验AFF和EFF微动脉不同的假设 网站。分离的AFF和EFF小动脉将在体外进行研究， 允许对DIAMETER响应进行视频监控 细胞内离子的激发波长荧光光谱分析 浓度和膜电位。我们将决定是否 AFF和EFF对Angii的微动脉反应不同于钙离子 进入要求，去极化的作用和起源，以及作用 依赖于IP3和蛋白激酶C的过程。预计 这些研究将揭示在功能上相关的区别 血管紧张素转换酶对肾小球前、后血管影响的决定因素 节段，以及提供有关荷尔蒙的进一步信息 离散型血管阻力调节中的相互作用 肾微循环网络的节段。

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.