Thirst deficits in rat model of aging

描述(申请人提供)：口渴感觉受损是脱水和液体平衡障碍的主要原因，这会给老年人带来严重的健康问题。导致脱水的体内水分和钠的损失会引起条件反射和行为反应，从而减缓这些物质的消耗速度，并最终恢复它们。这些条件反射和行为反应随着年龄的增长而明显下降。这些激素，血管紧张素II(Ang II)和醛固酮(Aldo)，以及由血管受体(如压力感受器)产生的神经信号，会刺激口渴(即喝水)和食盐(即钠摄取)，以响应水和钠的丧失。糖皮质激素显著增加水和钠的摄入量，对Ang II和Aldo做出反应。我们相当了解与年龄相关的肾脏和心血管功能损害如何导致老年伴随的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害。相比之下，我们缺乏对为什么荷尔蒙和神经信号机制未能促进老年人摄入足够的水和钠的理解，这减缓了药物和行为策略的发展，以补偿老年人口渴的感觉减弱和由此导致的液体摄入不足。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。这项拟议的研究将使用行为、生理、药理学和分子技术来研究荷尔蒙(Ang II、Aldo、糖皮质激素)和神经(血压/容量)信号之间的相互作用，这些信号控制着衰老大鼠的水和钠摄入。这些实验将产生关于控制水和钠摄取的基本生理机制的重要新信息，并恢复老龄动物的体液平衡。彻底了解这些行为和神经生物学过程将有助于生理(运动)和环境(高温)挑战下的正常个人的健康，有助于某些类型的与液体平衡(高血压、充血性心力衰竭)相关的病理疾病患者和老年人的健康。

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.