Thirst Deficits in Rat Model of Aging

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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.