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.
Dehydration is the most common cause of fluid and electrolyte disturbances in the elderly. Dehydration in the elderly is caused mainly by diminished sensations of thirst and, to a lesser extent, by diminished ability of the aging kidney to retain water and sodium in the body. 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.
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