title: Ionotropic glutamate receptors in paraventricular nucleus mediate adipose afferent reflex and regulate sympathetic outflow in rats.
abstract: OBJECTIVE
  Chemical stimulation of white adipose tissue (WAT) induces adipose afferent reflex (AAR) and results in increases in renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP). The enhanced AAR contributes to sympathetic activation and hypertension in obesity rats. This study was designed to investigate whether N-methyl-D-aspartate receptors (NMDAR) and non-NMDAR in paraventricular nucleus (PVN) modulate AAR and sympathetic outflow.
  
  
  METHODS
  Renal sympathetic nerve activity and MAP were recorded in anesthetized rats. AAR was evaluated by the RSNA and MAP responses to the injection of capsaicin into the four sites of right inguinal WAT (8.0 nmol for each site).
  
  
  RESULTS
  Bilateral PVN microinjection of NMDAR antagonist AP5 or MK-801, or non-NMDAR antagonist CNQX attenuated AAR, RSNA and MAP. AP5 + CNQX caused greater effects than AP5 or CNQX alone and almost abolished AAR. NMDAR agonist NMDA or non-NMDAR agonist AMPA enhanced the AAR, and increased RSNA and MAP, which were prevented by AP5 or CNQX pre-treatment respectively. Casein kinase 2 inhibitor DRB, NR2A antagonist NVP-AAM077 or NR2B antagonist CP-101,606 attenuated AAR, RSNA and MAP. NVP-AAM077 + CP-101,606 caused greater effects than NVP-AAM077 or CP-101,606 alone. Bilateral baroreceptor denervation and vagotomy enhanced AAR, which was abolished by PVN pre-treatment with AP5 + CNQX. Furthermore, AP5 + CNQX abolished the AAR induced by leptin in iWAT.
  
  
  CONCLUSIONS
  Both NMDAR and non-NMDAR in the PVN mediate AAR and contribute to the tonic control of sympathetic outflow and blood pressure. CK2, NR2A and NR2B subunits of NMDAR in the PVN are involved in the NMDAR-mediated tonic control of AAR, RSNA and MAP.
authors.affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: B-P
authors.initials: BP
authors.lastname: Cui
authors.forename: P
authors.initials: P
authors.lastname: Li
authors.forename: H-J
authors.initials: HJ
authors.lastname: Sun
authors.forename: L
authors.initials: L
authors.lastname: Ding
authors.forename: Y-B
authors.initials: YB
authors.lastname: Zhou
authors.forename: J-J
authors.initials: JJ
authors.lastname: Wang
authors.forename: Y-M
authors.initials: YM
authors.lastname: Kang
authors.forename: G-Q
authors.initials: GQ
authors.lastname: Zhu
mesh_terms: D052436:Adipose Tissue, White / Q000378:metabolism; D050154:Adiposity / Q000502:physiology; D000818:Animals; D001794:Blood Pressure; D008297:Male; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology*; D017207:Rats, Sprague-Dawley; D058468:Receptors, Ionotropic Glutamate / Q000378:metabolism*; D012018:Reflex / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology*
chemical_list: D058468:Receptors, Ionotropic Glutamate
keywords: blood pressure; glutamate receptor; paraventricule nucleus; sympathetic activity; white adipose tissue