title: Coping with dehydration: sympathetic activation and regulation of glutamatergic transmission in the hypothalamic PVN.
abstract: Autonomic and endocrine profiles of chronic hypertension and heart failure resemble those of acute dehydration. Importantly, all of these conditions are associated with exaggerated sympathetic nerve activity (SNA) driven by glutamatergic activation of the hypothalamic paraventricular nucleus (PVN). Here, studies sought to gain insight into mechanisms of disease by determining the role of PVN ionotropic glutamate receptors in supporting SNA and mean arterial pressure (MAP) during dehydration and by elucidating mechanisms regulating receptor activity. Blockade of PVN N-methyl-D-aspartate (NMDA) receptors reduced (P < 0.01) renal SNA and MAP in urethane-chloralose-anesthetized dehydrated (DH) (48 h water deprivation) rats, but had no effect in euhydrated (EH) controls. Blockade of PVN α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors had no effect in either group. NMDA in PVN caused dose-dependent increases of renal SNA and MAP in both groups, but the maximum agonist evoked response (Emax) of the renal SNA response was greater (P < 0.05) in DH rats. The latter was not explained by increased PVN expression of NMDA receptor NR1 subunit protein, increased PVN neuronal excitability, or decreased brain water content. Interestingly, PVN injection of the pan-specific excitatory amino acid transporter (EAAT) inhibitor DL-threo-β-benzyloxyaspartic acid produced smaller sympathoexcitatory and pressor responses in DH rats, which was associated with reduced glial expression of EAAT2 in PVN. Like chronic hypertension and heart failure, dehydration increases excitatory NMDA receptor tone in PVN. Reduced glial-mediated glutamate uptake was identified as a key contributing factor. Defective glutamate uptake in PVN could therefore be an important, but as yet unexplored, mechanism driving sympathetic hyperactivity in chronic cardiovascular diseases.
authors.affiliation: Department of Physiology and.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Bardgett
authors.affiliation: Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, Michigan.
authors.forename: Qing-Hui
authors.initials: QH
authors.lastname: Chen
authors.affiliation: Department of Physiology and.
authors.forename: Qing
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Department of Physiology and.
authors.forename: Alfredo S
authors.initials: AS
authors.lastname: Calderon
authors.affiliation: Department of Physiology and.
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Andrade
authors.affiliation: Department of Physiology and Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio, San Antonio, Texas; and Toney@uthscsa.edu.
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Toney
mesh_terms: D000223:Adaptation, Psychological / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003681:Dehydration / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005971:Glutamates / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology; D008297:Male; D023421:Models, Animal; D016202:N-Methylaspartate / Q000494:pharmacology; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D005971:Glutamates; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate
keywords: PVN; blood pressure; glutamate; sympathetic