Thirst deficits in rat model of aging

衰老大鼠模型的口渴缺陷

基本信息

批准号：
8720640
负责人：
ROBERT L THUNHORST
金额：
$ 24.76万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-06-01 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8720640
关键词：
Abbreviations Address Age Aging Agonist Aldosterone Angiotensin II Angiotensin II Receptor Animals Behavioral Blood Pressure Blood Vessels Blood Volume Body Fluids Cardiovascular Physiology Cardiovascular system Chemosensitization Chronic Congestive Heart Failure Dehydration Desire for food Development Disease Elderly Electrolytes Esthesia Excretory function Exercise Feeding behaviors Fluid Balance Glucocorticoids Goals Health Heating Homeostasis Hormonal Hormones Hypertension Hypesthesia Hypotension Impairment Individual Ingestion Investigation Kidney Knowledge Lead Liquid substance Literature Mediating Mineralocorticoids Modeling Molecular Nerve Neuraxis Neurobiology Patients Performance Personal Satisfaction Physiological Pressoreceptors Process Rattus Relative (related person)Renal function Research Signal Transduction Sodium Sodium Chloride Techniques Testing Therapeutic Thirst Water Work age related body water loss drinking drinking water juvenile animal novel prevent receptor relating to nervous system research study response restoration salt intake therapeutic development

项目摘要

DESCRIPTION (provided by applicant): Impaired sensations of thirst are the major cause of dehydration and disturbances of fluid balance that pose major health problems for the elderly. The losses of body water and sodium that cause dehydration evoke reflexive and behavioral responses that slow the rate of depletion of these substances and ultimately restore them. These reflexive and behavioral responses markedly decline with age. The hormones, angiotensin II (Ang II) and aldosterone (ALDO), and neural signals carried by nerves arising from vascular receptors (e.g., baroreceptors), stimulate thirst (i.e., water drinking) and salt appetite (i.e., sodium ingestion) in response to water and sodium loss. The glucocorticoid hormones dramatically increase the amounts of water and sodium that are ingested in response to Ang II and ALDO. We have considerable understanding of how age-related impairments in kidney and cardiovascular function contribute to the relative state of chronic dehydration that accompanies old age, and of the need for better therapeutic strategies to compensate for these impairments. In contrast, our lack of understanding of why hormonal and neural signaling mechanisms fail to promote adequate water and sodium ingestion in old age has slowed development of pharmacological and behavioral strategies to compensate for diminished sense of thirst and resulting inadequate fluid ingestion in the elderly. The present proposal builds upon the applicant's prior investigations of fluid-related afferent signaling and central processing. The proposed research will employ behavioral, physiological, pharmacological and molecular techniques to investigate interactions between hormonal (Ang II, ALDO, glucocorticoids) and neural (blood pressure/volume) signals that control water and sodium ingestion in a rat model of aging. These experiments will generate important new information about basic physiological mechanisms that control water and sodium ingestion and restore body fluid homeostasis in aging animals. A thorough understanding of these behavioral and neurobiological processes will contribute to the well-being of normal individuals exposed to physiological (exercise) and environmental (heat) challenges and of certain types of patients with pathological conditions related to fluid balance (hypertension; congestive heart failure) and the elderly.

描述（由申请人提供）：口渴感受损是脱水和体液平衡紊乱的主要原因，给老年人带来了重大健康问题。导致脱水的体内水和钠的流失会引起反射和行为反应，从而减缓这些物质的消耗速度并最终恢复它们。这些反射和行为反应随着年龄的增长而显着下降。血管紧张素 II (Ang II) 和醛固酮 (ALDO) 等激素以及血管受体（例如压力感受器）产生的神经携带的神经信号会刺激口渴（即喝水）和盐食欲（即摄入钠）。导致水和钠的流失。糖皮质激素会因 Ang II 和 ALDO 的作用而显着增加水和钠的摄入量。我们非常了解与年龄相关的肾脏和心血管功能损伤如何导致老年慢性脱水的相对状态，以及需要更好的治疗策略来补偿这些损伤。相比之下，我们对为什么激素和神经信号机制无法促进老年人摄入足够的水和钠缺乏了解，从而减缓了补偿老年人口渴感减弱和导致的液体摄入不足的药理学和行为策略的发展。本提案建立在申请人之前对流体相关传入信号和中央处理的研究的基础上。拟议的研究将采用行为、生理、药理学和分子技术来研究衰老大鼠模型中控制水和钠摄入的激素（Ang II、ALDO、糖皮质激素）和神经（血压/容量）信号之间的相互作用。这些实验将产生有关控制水和钠摄入并恢复衰老动物体液稳态的基本生理机制的重要新信息。彻底了解这些行为和神经生物学过程将有助于面临生理（运动）和环境（热）挑战的正常个体以及患有与体液平衡相关的病理状况（高血压、充血性心力衰竭）的某些类型患者的健康）和老人。