Extracellular Fluid Volume Homeostasis in Fish

随着动物的进化，细胞外液体被划分为血管内（血液）和间质（细胞之间）液体。血压调节和心血管功能密切依赖于血容量，由于液体可以在血液和间质室之间流动，间质液容量也影响血压。由于技术问题，在没有药物或手术的情况下，不可能在实验中操纵陆生脊椎动物的这些液体。拟议的研究将采用一种不同的动物模型，虹鳟鱼，来检查液体体积和心血管功能之间的相互关系。鳟鱼是这些研究的理想模型，因为它们自然生活在各种环境中，要么脱水，要么水合，盐负荷或盐消耗。我们也可以在其他更原始的鱼类，如盲鳗和鲨鱼身上测量液体隔间。虽然这些鱼不像鳟鱼那样能忍受环境的操纵，但它们提供了一个进化窗口，可以了解体液平衡与脊椎动物心血管系统之间关系的系统发育起源，以及影响它们发育的因素。在拟议的研究中，将在盲鳗、鲨鱼和虹鳟鱼中检查主要的液体室，血液、间质和细胞内，这些液体室生活在水、盐和渗透负荷独立控制的受控环境中。这些环境包括淡水、咸水、淡水加高盐饮食和高渗透压无盐水。此外，还将研究一种独特的流体隔室，即二次循环的性质。这种循环，可能是哺乳动物淋巴系统的进化原型，在任何鱼类中都没有被精确测量过。液体隔间将通过指示剂稀释法测量，使用特定的放射性标记物。一旦流体间室与水盐平衡之间的关系被确立，压力-容量调节系统、肾素血管紧张素系统、交感神经系统、抗利尿激素（精氨酸缩宫素）和利钠肽的作用将在水盐平衡改变的背景下被检查。这些实验将首次对任何鱼类的流体隔间进行完整的定量描述。他们也是第一次在脊椎动物身上进行实验，独立研究盐和水的平衡是如何调节的，以及这些参数是如何整合到心血管功能中的。这些研究在其他动物或非动物模型中是不可能的。从该项目获得的信息在心血管、肾脏和内分泌生理学的所有领域都是至关重要的，它适用于包括哺乳动物在内的所有脊椎动物。研究结果还将为开发压力较小的养鱼环境提供基线信息，从而具有实际效益。

As animals evolved, the extracellular fluids became compartmentalized into the intravascular (blood) and interstitial (between the cells) fluids. Blood pressure regulation and cardiovascular function is intimately dependent upon blood volume and, because fluids can move between blood and interstitial compartments, the interstitial fluid volume also influences blood pressure. Due to technical problems, it is impossible to experimentally manipulate these fluids in terrestrial vertebrates without drugs or surgery. The proposed research will employ a different animal model, the rainbow trout, to examine the interrelationships between fluid volumes and cardiovascular function. Trout are ideal models for these studies because they naturally live in a variety of environments that are either dehydrating or hydrating, and salt loading or salt depleting. Fluid compartments will also me measured in other, more primitive fish such as the hagfish and shark. While these fish do not tolerate manipulation of the environment as well as trout, they provide an evolutionary window into the phylogenetic origin of the relationships between fluid balance and the vertebrate cardiovascular system and the factors that shaped their development. In the proposed research, the primary fluid compartments, blood, interstitial, and intracellular, will be examined in hagfish and sharks and in rainbow trout living in controlled environments in which water, salt, and osmotic load are independently controlled. These environments include freshwater, saltwater, freshwater plus high salt diet, and high-osmolarity salt-free water. In addition, the nature of a unique fluid compartment, the secondary circulation, will be examined. This circulation, possibly the evolutionary prototype of the mammalian lymphatic system, has not been accurately measured in any fish. Fluid compartments will be measured by indicator dilution methods using specific radiolabelled markers. Once the relationships between fluid compartments and water and salt balance have been established, the role of pressure-volume regulatory systems, the renin angiotensin system, sympathetic nervous system, antidiuretic hormones (arginine vasotocin), and natriuretic peptides will be examined in the context of altered water and salt balance. These experiments will provide the first complete quantitative description of fluid compartments in any fish. They are also the first experiments, in any vertebrate, to independently examine how salt and water balance are regulated and how these parameters are integrated into cardiovascular function. These studies are not possible with other animal or non-animal models. The information obtained from the project is crucial in all areas of cardiovascular, renal and endocrine physiology and it is applicable to all vertebrates, including mammals. The results will also be of practical benefit by providing base-line information for development of less stressful environments for fish culture.