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.
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.
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|Santollo, Jessica; Torregrossa, Ann-Marie; Daniels, Derek (2017) Sex differences in the drinking response to angiotensin II (AngII): Effect of body weight. Horm Behav 93:128-136|
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|Daniels, Derek (2016) Angiotensin II (de)sensitization: Fluid intake studies with implications for cardiovascular control. Physiol Behav 162:141-6|
|Santollo, Jessica; Daniels, Derek (2015) Activation of G protein-coupled estrogen receptor 1 (GPER-1) decreases fluid intake in female rats. Horm Behav 73:39-46|
|MacLaren, D A A; Markovic, T; Daniels, D et al. (2015) Enhanced consumption of salient solutions following pedunculopontine tegmental lesions. Neuroscience 284:381-99|
|Santollo, Jessica; Daniels, Derek (2015) Multiple estrogen receptor subtypes influence ingestive behavior in female rodents. Physiol Behav 152:431-7|
|Gasparini, S; Menani, J V; Daniels, D (2015) Moxonidine into the lateral parabrachial nucleus modifies postingestive signals involved in sodium intake control. Neuroscience 284:768-74|
|Santollo, Jessica; Daniels, Derek (2015) Control of fluid intake by estrogens in the female rat: role of the hypothalamus. Front Syst Neurosci 9:25|
|McKay, Naomi J; Galante, Daniela L; Daniels, Derek (2014) Endogenous glucagon-like peptide-1 reduces drinking behavior and is differentially engaged by water and food intakes in rats. J Neurosci 34:16417-23|
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