Maintaining cardiovascular health relies on a number of physiological and behavioral mechanisms that monitor, respond to, and alleviate perturbations in body fluid homeostasis. Angiotensin II (AngII), the bioactive product of the renin-angiotensin system, is an important component of these actions, especially in the response to hypovolemia. AngII affects numerous systems including the kidney, adrenal gland, gastrointestinal tract, vascular smooth muscle, and brain. The central effects of AngII include increases in water and NaCl intake, critical behaviors for the maintenance of body fluid and cardiovascular homeostasis. These behavioral effects are mediated largely through AngII type 1 (AT1) receptors, which stimulate several intracellular signaling pathways including one that leads to increased inositol trisphosphate (IP3) formation and protein kinase C (PKC) activation, and another that increases phosphorylation of mitogen activated protein (MAP) kinase. Recent experiments suggest different relative contributions of these pathways to the water and NaCl intake induced by AngII. The experiments in the present proposal use behavioral, pharmacological, electrophysiological, molecular, and neuroanatomical approaches to explore the role of these intracellular signaling pathways in the control of AngII- induced water and NaCl. Specifically, the experiments will (1) determine the roles of the Gq/IP3/PKC and MAP kinase signaling pathways in AngII-induced water and NaCl intake;(2) determine the role of individual signaling pathways on neural activity at primary and downstream sites of AngII action in the brain;and (3) test the role of these signaling pathways and receptor phosphorylation on desensitization of the intracellular and behavioral responses after multiple treatments with AngII. These experiments use a multifaceted approach and a variety of techniques to answer these questions from behavioral, anatomical, electrophysiological, and neurochemical perspectives.

Public Health Relevance

Ingestion of water, salt, and food is critical for proper function of numerous body systems. Disorders related to energy and fluid imbalance include hypertension, obesity, heart disease, and diabetes. Understanding the neural mechanisms through which hormones mediate the ingestion of water, salt, and food may lead to novel therapeutic approaches to combat these relevant disease states.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Neuroendocrinology, Neuroimmunology, and Behavior Study Section (NNB)
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Maric-Bilkan, Christine
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State University of New York at Buffalo
Schools of Arts and Sciences
United States
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Speth, Robert C; Vento, Peter J; Carrera, Eduardo J et al. (2014) Acute repeated intracerebroventricular injections of angiotensin II reduce agonist and antagonist radioligand binding in the paraventricular nucleus of the hypothalamus and median preoptic nucleus in the rat brain. Brain Res 1583:132-40
Marshall, Anikó; Santollo, Jessica; Corteville, Caroline et al. (2014) Roux-en-Y gastric bypass does not affect daily water intake or the drinking response to dipsogenic stimuli in rats. Am J Physiol Regul Integr Comp Physiol 307:R114-20
Vento, Peter J; Daniels, Derek (2014) The anteroventral third ventricle region is critical for the behavioral desensitization caused by repeated injections of angiotensin II. Behav Brain Res 258:27-33
Santollo, Jessica; Marshall, Aniko; Daniels, Derek (2013) Activation of membrane-associated estrogen receptors decreases food and water intake in ovariectomized rats. Endocrinology 154:320-9
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Halpern, Casey H; Tekriwal, Anand; Santollo, Jessica et al. (2013) Amelioration of binge eating by nucleus accumbens shell deep brain stimulation in mice involves D2 receptor modulation. J Neurosci 33:7122-9
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Daniels, Derek (2010) Alan [corrected] N. Epstein award: Intracellular signaling and ingestive behaviors. Physiol Behav 100:496-502
Vento, Peter J; Daniels, Derek (2010) Repeated administration of angiotensin II reduces its dipsogenic effect without affecting saline intake. Exp Physiol 95:736-45