Thirst Deficits in Rat Model of Aging

描述(由申请人提供)：脱水包括体内水分的丧失。脱水会引起反射性和行为性反应，减缓水分流失的速度，最终恢复体内水分。为了激活适当的动态平衡反应，中枢神经系统必须接受和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。水平衡失调，包括脱水，是老年人的主要健康问题。老年人脱水的原因是肾脏在体内保持水分的能力受损，以及口渴的感觉受损。关于老年人肾脏和心血管功能的损害以及这些机制对老年伴随的相对脱水状态的贡献，人们已经有了一些理解。然而，老年人对参与体内平衡的行为机制的控制知之甚少。关于荷尔蒙和神经信号机制刺激老年人喝水的能力，人们知之甚少。本提案建立在申请人对流体相关的传入信号和中央处理的先前调查的基础上。这项拟议的研究将在大鼠中使用生理学、药理学、行为学和细胞学技术，允许研究相互作用的激素(血管紧张素、心钠素)和神经(血压/容量)传入信号，以控制衰老大鼠模型中的低血容量性和渗透性口渴。这些实验将产生关于维持和恢复老龄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，将有助于生理(运动)和环境(高温)挑战下的正常个人的健康，有助于某些类型患有与液体平衡(高血压、充血性心力衰竭)相关的病理疾病的患者的健康，以及老年人的健康。

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.