title: Essential role of RVL medullary neuronal activity in the long term maintenance of hypertension in conscious SHR.
abstract: BACKGROUND
  It is well established that sympathetic nervous system is responsible for the onset, development and maintenance of neurogenic hypertension. The rostroventrolateral medulla (RVLM) and medullo-cervical pressor area (MCPA) are important central sympathoexcitatory regions whose role on neurogenic hypertension remains unknown.
  
  
  OBJECTIVE
  To establish RVLM and MCPA roles in the long-term regulation of blood pressure by depressing their neuron activity through the over-expression of hKir2.1-potassium channel in conscious spontaneously hypertensive rats (SHR).
  
  
  METHODS
  In SHR, a lentiviral vector LVV-hKir2.1 was microinjected into RVLM or MCPA areas. A sham group was injected with LVV-eGFP. Blood pressure (BP) and heart rate (HR) were continuously monitored for 75 days. Baroreflex and chemoreflex functions were evaluated. Baroreflex gain, chemoreflex sensitivity, BP and HR variability were calculated.
  
  
  RESULTS
  LVV-hKir2.1 expression in RVLM, but not in MCPA, produced a significant time-dependent decrease in systolic, diastolic, mean-BP and LF of systolic BP at 60-days post-injection. No significant changes were seen in LVV-eGFP RVLM injected SHR.
  
  
  CONCLUSIONS
  Data show that chronic expression of Kir2.1 in the RVLM of conscious SHR caused a marked and sustained decrease in BP without changes in the baro- and peripheral chemoreceptor reflex evoked responses. This decrease was mostly due to a reduction in sympathetic output revealed indirectly by a decrease in the power density of the SBP-LF band. Our data are amongst the firsts to demonstrate the role of the RVLM in maintaining BP levels in hypertension in conscious SHR. We suggest that a decrease in RVLM neuronal activity is an effective anti-hypertensive treatment strategy.
authors.affiliation: Faculty of Medicine & Centro de Cardiologia of University of Lisbon, Portugal.
authors.forename: Vera
authors.initials: V
authors.lastname: Geraldes
authors.affiliation: Faculty of Medicine & Centro de Cardiologia of University of Lisbon, Portugal.
authors.forename: Nataniel
authors.initials: N
authors.lastname: Goncalves-Rosa
authors.affiliation: School of Physiology & Pharmacology, Medical Sciences Building, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: Beihui
authors.initials: B
authors.lastname: Liu
authors.affiliation: School of Physiology & Pharmacology, Medical Sciences Building, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: Julian F R
authors.initials: JF
authors.lastname: Paton
authors.affiliation: Faculty of Medicine & Centro de Cardiologia of University of Lisbon, Portugal. Electronic address: Isabelrocha@fm.ul.pt.
authors.forename: Isabel
authors.initials: I
authors.lastname: Rocha
mesh_terms: D000818:Animals; D017704:Baroreflex / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D001795:Blood Pressure Determination; D015153:Blotting, Western; D002940:Circadian Rhythm / Q000502:physiology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D007150:Immunohistochemistry; D016086:Lentivirus / Q000235:genetics; D008297:Male; D008526:Medulla Oblongata / Q000503:physiopathology*; D008991:Monitoring, Physiologic; D009474:Neurons / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism*; D011918:Rats, Inbred SHR
chemical_list: C489457:KCNJ2 protein, human; D024661:Potassium Channels, Inwardly Rectifying
keywords: Blood pressure; Hypertension; Lentiviral vector; Potassium channels (Kir2.1); Rostroventrolateral medulla; Spontaneously hypertensive rats (SHR); Sympathetic nervous system