title: NMDA Receptor Plasticity in the Hypothalamic Paraventricular Nucleus Contributes to the Elevated Blood Pressure Produced by Angiotensin II.
abstract: Hypertension induced by angiotensin II (Ang II) is associated with glutamate-dependent dysregulation of the hypothalamic paraventricular nucleus (PVN). Many forms of glutamate-dependent plasticity are mediated by NMDA receptor GluN1 subunit expression and the distribution of functional receptor to the plasma membrane of dendrites. Here, we use a combined ultrastructural and functional analysis to examine the relationship between PVN NMDA receptors and the blood pressure increase induced by chronic infusion of a low dose of Ang II. We report that the increase in blood pressure produced by a 2 week administration of a subpressor dose of Ang II results in an elevation in plasma membrane GluN1 in dendrites of PVN neurons in adult male mice. The functional implications of these observations are further demonstrated by the finding that GluN1 deletion in PVN neurons attenuated the Ang II-induced increases in blood pressure. These results indicate that NMDA receptor plasticity in PVN neurons significantly contributes to the elevated blood pressure mediated by Ang II.
authors.affiliation: Feil Family Brain and Mind Research Institute and mjg2003@med.cornell.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Glass
authors.affiliation: Feil Family Brain and Mind Research Institute and.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Feil Family Brain and Mind Research Institute and.
authors.forename: Christal G
authors.initials: CG
authors.lastname: Coleman
authors.affiliation: Feil Family Brain and Mind Research Institute and.
authors.forename: June
authors.initials: J
authors.lastname: Chan
authors.affiliation: Feil Family Brain and Mind Research Institute and.
authors.forename: Evgeny
authors.initials: E
authors.lastname: Ogorodnik
authors.affiliation: Feil Family Brain and Mind Research Institute and.
authors.forename: Tracey A
authors.initials: TA
authors.lastname: Van Kempen
authors.affiliation: Feil Family Brain and Mind Research Institute and Laboratory of Neuroendocrinology, The Rockefeller University, New York, New York 10065.
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Milner
authors.affiliation: Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, New York 10065, Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, and.
authors.forename: Scott D
authors.identifier: http://orcid.org/0000-0002-4580-7006
authors.initials: SD
authors.lastname: Butler
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, and.
authors.forename: Colin N
authors.initials: CN
authors.lastname: Young
authors.affiliation: Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, New York 10065, Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, and.
authors.forename: Robin L
authors.initials: RL
authors.lastname: Davisson
authors.affiliation: Feil Family Brain and Mind Research Institute and.
authors.forename: Costantino
authors.initials: C
authors.lastname: Iadecola
authors.affiliation: Feil Family Brain and Mind Research Institute and.
authors.forename: Virginia M
authors.identifier: http://orcid.org/0000-0001-9374-724X
authors.initials: VM
authors.lastname: Pickel
mesh_terms: D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000235:genetics*; D007839:Functional Laterality; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016253:Microscopy, Immunoelectron; D016202:N-Methylaspartate / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D010991:Plethysmography; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D014662:Vasoconstrictor Agents
chemical_list: C121673:Gprin1 protein, mouse; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D016194:Receptors, N-Methyl-D-Aspartate; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D049452:Green Fluorescent Proteins; D016202:N-Methylaspartate; D052248:Nitric Oxide Synthase Type I
keywords: gene deletion; gene therapy; hypertension; hypothalamus; synaptic plasticity