Physiology of Trout Natriuretic Peptides

这项研究将研究鱼中利钠肽(NPs)的生理学。NPS是一种多肽荷尔蒙家族，在几乎所有脊椎动物中都能减少血容量和降低血压。NPS于1981年在哺乳动物中首次被发现，尽管几个月后确定了它们的遗传密码，但它们的生理功能至今仍不清楚。这项建议质疑哺乳动物模型在NP研究中的适用性，因为哺乳动物通过蒸发和肾脏排泄不断失去水分，因此永远不会自然地使体积或压力超负荷。然而，淡水鱼(鲑鱼)的体积长期超载，作为最早的脊椎动物，包含NP家族的所有成员，它们构成了本研究的基础。最初，将为每个鲑鱼NP(ANP、CNP、VNP)开发特定的分析方法。这些测定将被用来确定通过使鲑鱼适应淡水(体积超载，盐分耗尽)、咸水(体积耗尽，盐分超载)和淡水+高盐饮食(体积和盐分超载)，独立地控制水和盐平衡，NP分泌是如何受到影响的。只有鲑鱼等泛盐生鱼类在所有这些条件下都能茁壮成长，它们是唯一一种这些参数可以独立、非侵入性和无压力地控制的脊椎动物。这些信息将被用来检验生理剂量的NPs对鲑鱼体液平衡、体内和体外心血管和肾脏功能的影响，并确定组织特有的NP分泌过程。这些研究将提供第一幅关于脊椎动物NP生理学的全面图景，它们最初是在脊椎动物中进化的。该项目是与加拿大和日本实验室的国际合作的一部分，它将为研究生提供国内外培训，并为本科生、中等教育教师和高中生提供国内培训。

This study will examine the physiology of natriuretic peptides (NPs) in fish. NPs are a family of peptide hormones that decrease blood volume and lower blood pressure in virtually all vertebrates. NPs were first identified in mammals in 1981and although their genetic code was determined a few months later, their physiological function remains unknown to the present time. This proposal questions the applicability of mammalian models in NP research because mammals continually lose water through evaporation and renal excretion and thus are never naturally volume or pressure over-loaded. However, freshwater fish (trout) are chronically volume over-loaded and as the earliest vertebrates that contain all members of the NP family of proteins, they form the basis for the present study. Initially, specific assays will be developed for each trout NP (ANP, CNP, VNP). These assays will be used to determine how NP secretion is affected by independently manipulating water and salt balance via adapting trout to freshwater (volume overload, salt depletion), saltwater (volume depletion, salt overload), and freshwater plus high salt diet (volume and salt overload). Only euryhaline fish, such as trout, thrive in all these conditions and they are the only vertebrates in which these parameters can be controlled independently, non-invasively, and without stress. This information will then be used to examine the effects of physiological doses of NPs on trout fluid balance, in vivo and in vitro cardiovascular and renal function, and identify tissue-specific NP secretory processes. These studies will provide the first comprehensive picture of NP physiology from the vertebrates in which they initially evolved. This project is part of an international collaboration with laboratories in Canada and Japan and it will provide domestic and foreign training for graduate students and domestic training for undergraduates, teachers in secondary education, and high school students.