Physiology of Trout Natriuretic Peptides

本研究将探讨鱼体内利钠肽（NPs）的生理特性。NPs是一种肽类激素，几乎在所有脊椎动物中都能减少血容量和降低血压。NPs于1981年首次在哺乳动物中被发现，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为人所知。该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，因此从未自然地体积或压力过载。然而，淡水鱼（鳟鱼）长期体积超载，作为最早含有NP家族蛋白所有成员的脊椎动物，它们构成了本研究的基础。最初，将为每种鳟鱼NP （ANP， CNP， VNP）开发特定的检测方法。这些试验将用于确定通过使鳟鱼适应淡水（体积过载，盐耗尽）、盐水（体积耗尽，盐过载）和淡水加高盐饮食（体积和盐过载）来独立操纵水盐平衡如何影响NP分泌。只有像鳟鱼这样的泛盐鱼类才能在所有这些条件下茁壮成长，它们是唯一可以独立控制这些参数的脊椎动物，非侵入性的，没有压力。这些信息随后将用于检查生理剂量的NP对鳟鱼体液平衡、体内和体外心血管和肾功能的影响，并确定组织特异性NP分泌过程。这些研究将提供NP生理学的第一个全面的图片，从脊椎动物，他们最初的进化。该项目是与加拿大和日本实验室国际合作的一部分，将为研究生提供国内和国外培训，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.