PMID- 24376743 OWN - NLM STAT- MEDLINE DCOM- 20150302 LR - 20211021 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 8 IP - 12 DP - 2013 TI - Superoxide anions in paraventricular nucleus modulate adipose afferent reflex and sympathetic activity in rats. PG - e83771 LID - 10.1371/journal.pone.0083771 [doi] LID - e83771 AB - 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 microl 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. FAU - Ding, Lei AU - Ding L AD - Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, China. FAU - Zhang, Ling-Li AU - Zhang LL AD - Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, China. FAU - Gao, Run AU - Gao R AD - Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, China. FAU - Chen, Dan AU - Chen D AD - Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, China. FAU - Wang, Jue-Jin AU - Wang JJ AD - Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, China. FAU - Gao, Xing-Ya AU - Gao XY AD - Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, China. FAU - Kang, Yu-Ming AU - Kang YM AD - Department of Physiology and Pathophysiology, Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an, Shanxi, China. FAU - Zhu, Guo-Qing AU - Zhu GQ AD - Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131223 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Acetophenones) RN - 0 (Cyclic N-Oxides) RN - 0 (Receptors, Ionotropic Glutamate) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 0 (Spin Labels) RN - 11062-77-4 (Superoxides) RN - 3WJQ0SDW1A (Polyethylene Glycols) RN - 6384-92-5 (N-Methylaspartate) RN - 6OTE87SCCW (6-Cyano-7-nitroquinoxaline-2,3-dione) RN - 76726-92-6 (2-Amino-5-phosphonovalerate) RN - 77521-29-0 (alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid) RN - B6J7B9UDTR (acetovanillone) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 1.15.1.1 (polyethylene glycol-superoxide dismutase) RN - S07O44R1ZM (Capsaicin) RN - U78ZX2F65X (tempol) SB - IM MH - 2-Amino-5-phosphonovalerate/pharmacology MH - 6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacology MH - Acetophenones/pharmacology MH - Adipose Tissue, White/drug effects/*metabolism MH - Animals MH - Capsaicin/pharmacology MH - Cyclic N-Oxides/pharmacology MH - Male MH - N-Methylaspartate/pharmacology MH - Paraventricular Hypothalamic Nucleus/drug effects/*metabolism/physiology MH - Polyethylene Glycols/pharmacology MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Ionotropic Glutamate/metabolism MH - Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/metabolism MH - *Reflex/drug effects MH - Spin Labels MH - Superoxide Dismutase/pharmacology MH - Superoxides/*metabolism MH - Sympathetic Nervous System/drug effects/*physiology MH - alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/pharmacology PMC - PMC3871588 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2014/01/01 06:00 MHDA- 2015/03/03 06:00 PMCR- 2013/12/23 CRDT- 2013/12/31 06:00 PHST- 2013/08/10 00:00 [received] PHST- 2013/11/08 00:00 [accepted] PHST- 2013/12/31 06:00 [entrez] PHST- 2014/01/01 06:00 [pubmed] PHST- 2015/03/03 06:00 [medline] PHST- 2013/12/23 00:00 [pmc-release] AID - PONE-D-13-33038 [pii] AID - 10.1371/journal.pone.0083771 [doi] PST - epublish SO - PLoS One. 2013 Dec 23;8(12):e83771. doi: 10.1371/journal.pone.0083771. eCollection 2013.