REGULATION OF SINGLE CAPILLARY PERMEABILITY PROPERTIES

毛细管水和溶质运移一直被认为是被动的 流程. 我们实验室最近的单毛细管研究表明， 在正常条件下可以主动调节血管渗透性。 中心假设是，分隔循环血液的屏障 不是一个静态的分区，而是具有快速 并响应于变化而选择性地改变水和溶质渗透性 in the local本地environment环境. 我们的总体目标是确定 由此微血管渗透性特性响应于 生理刺激 这些研究将单独进行 两栖动物和哺乳动物的灌注毛细血管， 控制压力，定义灌注液和灌注液溶液， 血管表面积是恒定的。 仓鼠的哺乳动物研究 （中仓鼠）肠系膜微血管，将测试是否交换 血管特性类似于两栖动物模型青蛙（蛙 pipiens）肠系膜微血管。 因此，测试的一般性， 结果 建议对分离的内皮细胞进行进一步研究， 将我们的单血管发现与细胞水平的发现联系起来， 检测内皮细胞是否为控制屏障的成分 功能经血管水运动将通过改良的 Landis技术;将通过显微荧光测定法测量溶质移动。 在 将在按流量分类的容器中评估成对实验的运输 微动脉、真毛细血管或微静脉毛细血管的模式，首先受到控制 在规定的试验条件下。 未来五 年，我们将直接测试以下假设：1）交换船只 保持在中间（激活）状态，并具有连续性 因此，多个因素决定了血管的水平 活化以及血管可改变渗透性的程度， 因此，2）穿过内皮细胞的钙的腔跨膜通量 细胞表面是激活状态的主要决定因素，和3）体液 试剂急剧地和可逆地改变渗透性性质， 激活的船只 这些假设的解决将提供额外的 了解短期或急性控制全身的机制 交换脉管系统中的水和溶质分布。 长远 肱骨和非常快的神经介导的稳态机制， 更好地研究。 很少有工作已经做了调查， 短期（分钟至小时）监管的监管特点 交换屏障水平的液体平衡。 的能力 调节微血管交换特性，沿着改变 Starling部队，将允许快速，选择性和局部变化， 交换能力，以维持体内平衡。

Capillary water and solute transport have been regarded to be passive processes. Recent single capillary studies from our laboratory suggest vascular permeability can be actively regulated under normal conditions. The central hypothesis is that the barrier separating circulating blood from tissue is not a static partition but possesses the ability to rapidly and selectively alter water and solute permeability in response to changes in the local environment. Our overall aim is to determine the mechanisms whereby microvascular permeability properties are altered in response to physiological stimuli. These studies will be conducted in individually perfused capillaries of amphibia and mammalia where hydrostatic and osmotic pressures were controlled, perfusate and suffusate solutions defined and vascular surface area is constant. The mammalian studies on hamster (mesocricetus auratus) mesenteric microvessel, will test whether exchange vessel properties are similar to those in the amphibian model, frog (rana pipiens) mesenteric microvessels. Thus, testing the generality of the results. Additional studies, with isolated endothelia, are proposed to bridge our single vessel findings with those at the cellular level and will test whether the endothelial cell is the component controlling barrier function. Transvascular water movement will be measured by the modified Landis technique; solute movement will be measured by microfluorometry. In paired experiments transport will be assessed in vessels classified by flow pattern as arteriolar, true or venular capillaries, first under control conditions, then under specified test conditions. During the next five years we will test directly the following hypotheses: 1) Exchange vessels are maintained at an intermediate (activated) state and possess a continuum of sensitivity thus, multiple factors determine the level of vessel activation as well as the degree to which a vessel may alter permeability, thus 2) The luminal trans-membrane flux of calcium across the endothelial cell surface is the major determinant of activation state, and 3) Humoral agents acutely and reversibly modify the permeability properties of an activated vessel. Resolution of these hypotheses will provide additional insight into the mechanisms of short term or acute control of whole body water and solute distribution in the exchange vasculature. The longer term humeral and the very fast neurally mediated homeostatic mechanisms have been better studied. Very little work has been done to investigate the regulatory features in the short term (minutes to hours) regulation of fluid balance at the level of the exchange barrier. The ability to regulate microvessel exchange properties, along with the ability to alter Starling Forces, would allow for rapid, selective and local changes in the exchange capacity to maintain homeostasis.