title: Oxidative stress in the rostral ventrolateral medulla modulates excitatory and inhibitory inputs in spontaneously hypertensive rats.
abstract: OBJECTIVE
  The rostral ventrolateral medulla (RVLM) of the brainstem and the paraventricular nucleus (PVN) of the hypothalamus play crucial roles in central cardiovascular regulation. In hypertensive rats, an imbalance of excitatory and inhibitory inputs to the RVLM enhances central sympathetic outflow. Increased reactive oxygen species (ROS) in the RVLM also contribute to sympathoexcitation, leading to hypertension. The aim of the present study was to elucidate whether ROS in the RVLM modulate synaptic transmission via excitatory and inhibitory amino acids and influence the excitatory inputs to the RVLM from the PVN in spontaneously hypertensive rats (SHRs).
  
  
  RESULTS
  We transfected adenovirus vectors encoding the manganese superoxide dismutase (AdMnSOD) gene to scavenge ROS in the RVLM both in Wistar-Kyoto rats and SHRs. The decreases in blood pressure and renal sympathetic nerve activity (RSNA) evoked by injecting kynurenic acid, a glutamate receptor blocker, into the RVLM were attenuated, and the increases in blood pressure and RSNA evoked by injecting bicuculline, a γ-amino butyric acid (GABA) receptor blocker, into the RVLM were enhanced in AdMnSOD-transfected SHRs compared with adenovirus vectors encoding the β-galactosidase (AdLacZ) gene-transfected SHRs. Furthermore, the increases in blood pressure and RSNA evoked by injecting bicuculline into the PVN were attenuated in AdMnSOD-transfected SHRs compared with AdLacZ-transfected SHRs.
  
  
  CONCLUSIONS
  These findings suggest that ROS in the RVLM enhance glutamatergic excitatory inputs and attenuate GABAergic inhibitory inputs to the RVLM, thereby increasing sympathoexcitatory input to the RVLM from the PVN in SHRs.
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Nishihara
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hirooka
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Matsukawa
authors.forename: Takuya
authors.initials: T
authors.lastname: Kishi
authors.forename: Kenji
authors.initials: K
authors.lastname: Sunagawa
mesh_terms: D000818:Animals; D001794:Blood Pressure; D006339:Heart Rate; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D007668:Kidney / Q000294:innervation; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism* / Q000503:physiopathology; D018384:Oxidative Stress; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017382:Reactive Oxygen Species / Q000378:metabolism; D018079:Receptors, GABA / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D018079:Receptors, GABA; D017470:Receptors, Glutamate; D013482:Superoxide Dismutase