Thirst Deficits in Rat Model of Aging

衰老大鼠模型中的口渴缺陷

• 批准号: 7061658
• 负责人: ROBERT L THUNHORST
• 金额: $ 23.62万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7061658
• 关键词: age difference; aging; angiotensin II; animal old age; atrial natriuretic peptide; baroreceptors; biological models; biological signal transduction; blood chemistry; blood pressure; blood volume; body fluids; body water dehydration; homeostasis; hormone regulation /control mechanism; immunocytochemistry; juvenile animal; laboratory rat; longitudinal animal study; neural information processing; neuroregulation; osmotic pressure; renin angiotensin system; thirst; urinalysis; water drinking behavior

DESCRIPTION (provided by applicant): Dehydration involves loss of body water. Dehydration elicits reflexive and behavioral responses that slow the rate of water loss and ultimately restore body water. In order for appropriate homeostatic responses to be activated, the central nervous system must receive and integrate multiple types of sensory input from specialized receptors that monitor the status of body fluids. This afferent information includes humoral signals carried by the blood and neural signals arising from vascular receptors carried by nerves. Disturbances of water balance, including dehydration, are major health problems in the elderly. Dehydration in the elderly results from impairments in the ability of the kidney to retain water in the body, and impaired sensations of thirst. There is some understanding regarding impairments in renal and cardiovascular function in the elderly and the contributions of these mechanisms to the relative state of dehydration that is known to accompany old age. However, little is known in the elderly about control of the behavioral mechanisms that are involved in volume homeostasis. There is remarkably little knowledge about the ability of hormonal and neural signaling mechanisms to stimulate water drinking 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 physiological, pharmacological, behavioral, and cellular techniques in the rat that permit the investigation of interactive hormonal (angiotensin, atrial natriuretic peptide) and neural (blood pressure/volume) afferent signals that control hypovolemic and osmotic thirst in a rat model of aging. These experiments will generate important new information about basic physiological mechanisms that maintain and restore body fluid homeostasis in aging animals. Increased understanding of these 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), as well as the well being of the elderly.

描述（由申请人提供）：脱水涉及体内水分的流失。脱水会引起反射和行为反应，从而减缓水分流失的速度并最终恢复体内水分。为了激活适当的稳态反应，中枢神经系统必须接收并整合来自监测体液状态的专门受体的多种类型的感觉输入。这种传入信息包括血液携带的体液信号和神经携带的血管受体产生的神经信号。水平衡紊乱，包括脱水，是老年人的主要健康问题。老年人脱水是由于肾脏保留体内水分的能力受损以及口渴感受损造成的。人们对老年人肾功能和心血管功能受损以及这些机制对老年时相对脱水状态的影响有一些了解。然而，老年人对参与容量稳态的行为机制的控制知之甚少。关于激素和神经信号机制刺激老年人喝水的能力知之甚少。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。拟议的研究将在大鼠中采用生理学、药理学、行为和细胞技术，从而研究控制大鼠低血容量和渗透性口渴的相互作用的激素（血管紧张素、心房钠尿肽）和神经（血压/容量）传入信号衰老模型。这些实验将产生有关维持和恢复衰老动物体液稳态的基本生理机制的重要新信息。增加对这些神经生物学过程的了解将有助于面临生理（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）的某些类型患者的福祉，例如以及老年人的福祉。