Thirst deficits in rat model of aging

描述（由申请人提供）：口渴感觉受损是造成脱水和体液平衡紊乱的主要原因，对老年人构成重大健康问题。身体水分和钠的流失会引起脱水，从而引起反射性和行为反应，减缓这些物质的消耗速度，并最终恢复它们。这些自反性和行为反应随着年龄的增长而显著下降。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）产生的神经传递的神经信号，刺激口渴（即饮水）和盐的食欲（即钠的摄入），以应对水和钠的损失。糖皮质激素对Ang II和ALDO的反应会显著增加摄入的水和钠的量。我们对肾脏和心血管功能的年龄相关损伤如何导致伴随老年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伤有了相当的了解。相比之下，我们对为什么激素和神经信号机制不能促进老年人摄入足够的水和钠的理解不足，这延缓了药理学和行为策略的发展，以补偿老年人口渴感的减弱和由此导致的液体摄入不足。本提案建立在申请人先前对流体相关传入信号和中央处理的调查之上。拟议的研究将采用行为学、生理学、药理学和分子技术来研究激素（Ang II、ALDO、糖皮质激素）和神经（血压/容积）信号之间的相互作用，这些信号控制着衰老大鼠模型中水和钠的摄入。这些实验将为老龄动物控制水钠摄入和恢复体液平衡的基本生理机制提供重要的新信息。对这些行为和神经生物学过程的透彻理解将有助于正常个体在生理（运动）和环境（热）挑战下的健康，以及某些类型的与体液平衡相关的病理状况（高血压、充血性心力衰竭）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.