Superoxide anions in paraventricular nucleus modulate adipose afferent reflex and sympathetic activity in rats

PLoS One. 2013 Dec 23;8(12):e83771. doi: 10.1371/journal.pone.0083771. eCollection 2013.

Abstract

Background: Adipose afferent reflex (AAR) is a sympatho-excitatory reflex induced by chemical stimulation of white adipose tissue (WAT). Ionotropic glutamate receptors including NMDA receptors (NMDAR) and non-NMDA receptors (non-NMDAR) in paraventricular nucleus (PVN) mediate the AAR. Enhanced AAR contributes to sympathetic activation and hypertension in obesity rats. This study was designed to investigate the role and mechanism of superoxide anions in PVN in modulating the AAR.

Methodology/principal findings: Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in anesthetized rats. AAR was evaluated by the RSNA and MAP responses to injections of capsaicin into four sites of right inguinal WAT (8.0 nmol in 8.0 µl for each site). Microinjection of polyethylene glycol-superoxide dismutase (PEG-SOD), the superoxide anion scavenger tempol or the NAD(P)H oxidase inhibitor apocynin into the PVN decreased the baseline RSNA and MAP, and attenuated the AAR. Unilateral WAT injection of capsaicin increased superoxide anions in bilateral PVN, which was prevented by the WAT denervation. WAT injection of capsaicin increased superoxide anion level and NAD(P)H oxidase activity in the PVN, which was abolished by the PVN pretreatment with the combined NMDAR antagonist AP5 and non-NMDAR antagonist CNQX. Microinjection of the NMDAR agonist NMDA or the non-NMDAR agonist AMPA increased superoxide anion level and NAD(P)H oxidase activity in the PVN.

Conclusions: NAD(P)H oxidase-derived superoxide anions in the PVN contributes to the tonic modulation of AAR. Activation of ionotropic glutamate receptors in the PVN is involved in the AAR-induced production of superoxide anions in the PVN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Amino-5-phosphonovalerate / pharmacology
  • 6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
  • Acetophenones / pharmacology
  • Adipose Tissue, White / drug effects
  • Adipose Tissue, White / metabolism*
  • Animals
  • Capsaicin / pharmacology
  • Cyclic N-Oxides / pharmacology
  • Male
  • N-Methylaspartate / pharmacology
  • Paraventricular Hypothalamic Nucleus / drug effects
  • Paraventricular Hypothalamic Nucleus / metabolism*
  • Paraventricular Hypothalamic Nucleus / physiology
  • Polyethylene Glycols / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Ionotropic Glutamate / metabolism
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Reflex* / drug effects
  • Spin Labels
  • Superoxide Dismutase / pharmacology
  • Superoxides / metabolism*
  • Sympathetic Nervous System / drug effects
  • Sympathetic Nervous System / physiology*
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology

Substances

  • Acetophenones
  • Cyclic N-Oxides
  • Receptors, Ionotropic Glutamate
  • Receptors, N-Methyl-D-Aspartate
  • Spin Labels
  • Superoxides
  • Polyethylene Glycols
  • N-Methylaspartate
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • 2-Amino-5-phosphonovalerate
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • acetovanillone
  • Superoxide Dismutase
  • polyethylene glycol-superoxide dismutase
  • Capsaicin
  • tempol

Grants and funding

This work was supported by Chinese National Natural Science fund (31171095 and 31271213), National Basic Research Program of China (973 Program, No. 2012CB517805). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.