Extracellular Fluid Volume Homeostasis in Fish

随着动物的进化，细胞外的液体被分割成血管内(血液)和间质(细胞之间)的液体。血压调节和心血管功能密切依赖于血容量，因为液体可以在血液和间质之间流动，所以间质液体容量也会影响血压。由于技术问题，在没有药物或手术的情况下，不可能在陆地脊椎动物身上实验操作这些液体。这项拟议的研究将使用一种不同的动物模型--彩虹鲑鱼--来研究体液量和心血管功能之间的相互关系。鲑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，要么缺水，要么盐分增加，要么盐分耗尽。液体隔间也将在其他更原始的鱼类中进行测量，如八目鳗和鲨鱼。虽然这些鱼不像鲑鱼那样耐受环境的操纵，但它们为流体平衡与脊椎动物心血管系统之间的关系以及影响它们发育的因素的系统起源提供了一个进化窗口。在这项拟议的研究中，主要的液体隔室，即血液、间质和细胞内，将在鳗鱼和鲨鱼以及生活在水、盐和渗透负荷独立控制的受控环境中的彩虹鲑鱼中进行检查。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，还将检查一种独特的流体隔间--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，在任何鱼类身上都没有被准确测量过。液体舱将通过使用特定的放射性标记的指示剂稀释法进行测量。一旦建立了液体隔室和水盐平衡之间的关系，将在水盐平衡改变的背景下研究压力-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(精氨酸血管催产素)和利钠肽的作用。这些实验将首次对任何鱼类的体液隔间进行完整的定量描述。这也是在任何脊椎动物中，第一次独立检查盐和水平衡是如何调节的，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上是不可能的。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，它适用于所有脊椎动物，包括哺乳动物。研究结果还将为开发压力较小的鱼类养殖环境提供基线信息，从而产生实际效益。

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.