Thirst deficits in rat model of aging

衰老大鼠模型的口渴缺陷

• 批准号: 8330773
• 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
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8330773
• 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

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）：口渴的感觉受损是脱水和流体平衡干扰的主要原因，这对老年人构成了重大健康问题。导致脱水的体水和钠的损失引起了反射性和行为反应，从而减慢了这些物质的耗尽速度并最终恢复它们。这些反思性和行为反应随着年龄的增长而显着下降。激素，血管紧张素II（ANG II）和醛固酮（Aldo）以及由血管受体（例如压力感受器）引起的神经携带的神经信号，刺激对水和钠损失响应的渴求（即水饮用）和盐的食欲（即盐的食欲）。糖皮质激素激素大大增加了响应Ang II和Aldo摄入的水和钠的量。我们对肾脏和心血管功能中与年龄相关的损害有很大的了解有助于老年伴随的慢性脱水状态，以及需要更好的治疗策略来补偿这些障碍。相反，我们缺乏对为什么激素和神经信号传导机制在老年中无法促进足够的水和钠摄入的原因减慢了药理学和行为策略的发展，以补偿老年人的口渴感下降，并导致老年人的液体摄入不足。本提案建立在申请人对流体相关传入信号和中央处理的先前调查的基础上。拟议的研究将采用行为，生理，药理和分子技术来研究激素（Ang II，Aldo，糖皮质激素）与神经（血压/体积）信号之间的相互作用，以控制老鼠模型中的水和摄入钠。这些实验将生成有关控制水和摄入水的基本生理机制的重要新信息，并恢复衰老动物中的体液稳态。对这些行为和神经生物学过程的透彻理解将有助于对暴露于生理（运动）和环境（热）挑战的正常人以及与液体平衡有关的病理状况（高血压；充血性心力衰竭）和老年人的某些类型的患者。