Extracellular Fluid Volume Homeostasis in Fish

随着动物的进化，细胞外液被划分为血管内（血液）和间质（细胞间）液。 血压调节和心血管功能密切依赖于血容量，并且由于液体可以在血液和间质室之间移动，所以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，不可能在陆生脊椎动物中实验性地操纵这些流体。 拟议的研究将采用不同的动物模型，虹鳟鱼，以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脱水或水合，盐负荷或盐消耗的环境中。 其他更原始的鱼类，如盲鳗和鲨鱼，也可以测量它们的液体室。 虽然这些鱼不容忍操纵的环境，以及鳟鱼，他们提供了一个进化的窗口到流体平衡和脊椎动物心血管系统之间的关系的系统发育的起源和因素，塑造了他们的发展。 在拟议的研究中，主要的流体室，血液，间质和细胞内，将检查在盲鳗和鲨鱼和虹鳟鱼生活在受控环境中，其中水，盐和渗透负荷是独立控制。 这些环境包括淡水、盐水、淡水加高盐饮食和高渗透压无盐水。 此外，一个独特的流体隔室，二次循环的性质，将被检查。 这种循环，可能是哺乳动物淋巴系统的进化原型，尚未在任何鱼类中准确测量。 将使用特定放射性标记物通过指示剂稀释法测量液体隔室。 一旦建立了液体室与水盐平衡之间的关系，将在改变水盐平衡的背景下检查压力-容积调节系统、肾素血管紧张素系统、交感神经系统、抗利尿激素（精氨酸血管紧张素）和利钠肽的作用。 这些实验将提供第一个完整的定量描述流体隔间在任何鱼类。 它们也是第一个在任何脊椎动物中独立研究盐和水平衡如何调节以及这些参数如何整合到心血管功能中的实验。 这些研究不可能使用其他动物或非动物模型。 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至关重要，适用于所有脊椎动物，包括哺乳动物。 这些结果也将通过提供基线信息为鱼类养殖提供更少的压力环境，从而具有实际意义。

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.