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.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Neuroendocrinology, Neuroimmunology, and Behavior Study Section (NNB)
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Mackiewicz, Miroslaw
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University of Iowa
Schools of Arts and Sciences
Iowa City
United States
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Hardy, Rachel N; Simsek, Zinar D; Curry, Brandon et al. (2018) Aging affects isoproterenol-induced water drinking, astrocyte density, and central neuronal activation in female Brown Norway rats. Physiol Behav 192:90-97
Xue, Baojian; Yu, Yang; Zhang, Zhongming et al. (2016) Leptin Mediates High-Fat Diet Sensitization of Angiotensin II-Elicited Hypertension by Upregulating the Brain Renin-Angiotensin System and Inflammation. Hypertension 67:970-6
Thunhorst, Robert L; Xue, Baojian; Beltz, Terry G et al. (2015) Age-related changes in thirst, salt appetite, and arterial blood pressure in response to aldosterone-dexamethasone combination in rats. Am J Physiol Regul Integr Comp Physiol 308:R807-15
Johnson, Ralph F; Beltz, Terry G; Johnson, Alan Kim et al. (2015) Effects of fludrocortisone on water and sodium intake of C57BL/6 mice. Am J Physiol Regul Integr Comp Physiol 309:R247-54
Xu, Jie; Johnson, Alan Kim; Thunhorst, Robert L (2015) Thirst and sodium appetite in rats with experimental nephrotic syndrome. Physiol Behav 149:317-23
Thunhorst, Robert L; Beltz, Terry; Johnson, Alan Kim (2014) Age-related declines in thirst and salt appetite responses in male Fischer 344√óBrown Norway rats. Physiol Behav 135:180-8
Thunhorst, Robert L; Beltz, Terry G; Johnson, Alan Kim (2013) Effects of aging on mineralocorticoid-induced salt appetite in rats. Am J Physiol Regul Integr Comp Physiol 305:R1498-505
Thunhorst, Robert L; Grobe, Connie L; Beltz, Terry G et al. (2011) Effects of ?-adrenergic receptor agonists on drinking and arterial blood pressure in young and old rats. Am J Physiol Regul Integr Comp Physiol 300:R1001-8
Thunhorst, Robert L; Beltz, Terry G; Johnson, Alan Kim (2010) Drinking and arterial blood pressure responses to ANG II in young and old rats. Am J Physiol Regul Integr Comp Physiol 299:R1135-41
De Gobbi, Juliana I F; Beltz, Terry G; Johnson, Ralph F et al. (2009) Non-NMDA receptors in the lateral parabrachial nucleus modulate sodium appetite. Brain Res 1301:44-51

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